Process for preparing fluorobenzene and benzoic acid hypofluorite

ABSTRACT

The invention relates to a use of a fluorination gas, the elemental fluorine (F2) is preferably present in a high concentration, e.g. in a concentration of elemental fluorine (F2), especially of equal to much higher than 15% or even 20% by volume (i.e., at least 15% or even 20% by volume), and to a process for the manufacture of a fluorinated benzene starting from benzoic acid by direct fluorination employing a fluorination gas. The elemental fluorine (F2) is preferably present in high concentration, and subsequent decarboxylation of the benzoic acid hypofluorite obtained by direct fluorination. The process of the invention is also directed to the manufacture of benzoic acid hypofluorite by direct fluorination of benzoic acid. Especially the invention is of interest in the preparation of fluorinatedbenzene, final products and as well intermediates, for usage in agro-, pharma-, electronics-, catalyst, solvent and other functional chemical applications.

BACKGROUND OF THE INVENTION Field of the Disclosure

The invention relates to process for the manufacture or preparation offluorinated benzene, in particular monofluorobenzene, using afluorination gas comprising elemental fluorine (F₂) in a step of thesaid process. The process of the invention, for example, can comprise abatch or continuous manufacture or preparation of fluorinated benzene,in particular monofluorobenzene, using fluorination gas comprisingelemental fluorine (F₂). The invention also relates to a new process forthe manufacture or preparation of benzoic acid hypofluorite. Also, thislatter process of the invention, for example, can comprise a batch orcontinuous manufacture or preparation of benzoic acid hypofluorite,using fluorination gas comprising elemental fluorine (F₂).

Description of Related Art

Fluorobenzene is still prepared by Balz-Schiemann, Sandmeyer or HalexReaction. All this types of reactions deliver good yields but are notenvironmental friendly at all. Especially in Asia plants are closed byauthorities due to environmental problems which cannot be solved by thistype of chemistries. It is known that carboxylic acids can befluorinated and photolytic decarboxylated like in J. Am. Chem. Soc.2015137175654-5657 (https://doi.org/10.1021/jacs.5b02244). But thedescribed F-source (e.g. Selectfluor) is extremely expensive and NOTcommercially available in large industrial volumes needed forfluorobenzene. A huge drawback is the huge sceleton of Selectfluorcarrying the F-atom, and this sceleton cannot be recycled and so farneed to be incinerated. It is obvious that this described method is newbut not feasible in industrial scale and regarding environmentalaspects, even worse than Balz-Schiemann and Sandmeyer reactions. Also asophisticated Ir-based photocatalyst is necessary which is another bigdrawback. No information about equipment is given as chemistryespecially photochemistry with fluorinated compounds need very specialdedicated equipment due to fluoride corrosion at all glassware alreadyin lab but even much more important in industrial scale. The usage ofcyanuric fluoride (2,4,6-trifluoro-1,3,5-triazine) like describedalready in early days in Synthesis 8, 487-8 (1973) is also not anindustrial workable option not even for the first step to preparefluorobenzene.

Fluorinated organic compounds in industrial scale are prepared byfluorine halogen exchange using anhydrous HF, addition of HF to olefinicdouble bonds, fluorinating agents like amine x nHF, electrofluorinationwith HF (in situ generation of F₂) where in latter case selectivity,scalability and missing environmental friendliness (formation of verytoxic partial fluorinated compounds) often is and remains an unsolvedproblem. Another existing fluorination procedure is using F₂-gasdirectly. But this requires—besides availability of industrialquantities—the very skilled handling of F₂-gas and co-produced HF(hydrogen (H) vs. fluorine (F) exchange reaction).

Elemental fluorine (F₂) is a yellow compressed gas (fluorine gas,F₂-gas) with a pungent odor; it is a strong oxidant, reacts violentlywith combustible and reducing substances. Due to its strong chemicalactivity, and therefore, the need of equipment and containers withstrong corrosion resistance to fluorine and HF, F₂-gas is usually mixedwith nitrogen (N₂). In Europe, usually only mixtures of 95% N2 with only5% F₂-gas are allowed to be transported, or with exemption permissiononly of up to 10% content of F₂-gas.

In Asia, a ratio up to 20% F₂-gas in inert gas like N₂ is available.

Such dilution of F₂-gas by inert gas like N₂ is necessary because ofsafety and reducing and/or controlling the chemical activity orreactivity of F₂-gas in chemical reactions. However, this dilution ofF₂-gas by inert gas needed for the said reason of “deactivation” inindustrial scale has the disadvantage that on the one side the dosing ofF₂-gas diluted by inert gas is very challenging, and on the other sideeven more important as drawback, that the heat transfer in reactorequipment during chemical reactions with F₂-gas, as these reaction arevery exothermic, is very much reduced by inert gas, and due to thediluting inert gas is resulting in reduced heat transfer, and in worstcase might even cause runaways. Hence, in principle the inert gas isundesirably functioning as insulation gas.

It is known in the prior art to fluorinate deactivated benzenederivatives with a diluted fluorination gas, e.g., in Chambers et al.(Journal of Fluorine Chemistry 128 (2007) 29-33). Chambers is using as afluorination gas containing 10% (vol.-%) elemental fluorine (F₂) innitrogen (N₂) as inert gas, and is using solvents for the reaction,e.g., acetonitrile or formic acid reaction media. Chambers is reportingdirect fluorination reactions of 1,4-disubstitutedaromatic systemsbearing an electron withdrawing and releasing group, using microreactortechnology. The fluorinated products are obtained by a processconsistent with an electrophilic substitution process due to thesolvents used. Thus, high selectivity and yields of monofluorinatedproducts are reported by Chambers when using either acetonitrile orformic acid reaction media. It is known in the prior art that highrelative permittivity solvents or protonic acids can be used veryeffectively for the fluorination of aromatic systems because, in thesemedia, the fluorine molecule is rendered more susceptible towardsnucleophilic attack by interaction with the solvent while competing freeradical processes are minimized. However, in the process described byChambers, typically, reactions are carried out only in small scalereactions, for example over a 16 h period enabling 5 to 10 g of crudeproduct to be collected.

Also, Chambers tested in the same experimental setting as described hereabove, the direct fluorination of aromatic rings bearing two strongelectron withdrawing groups, which aromatic rings are, of course,relatively unreactive towards electrophilic attack. However, reactionsbetween such substrates and elemental fluorine (F₂), i.e., using thefluorination gas containing 10% (vol.-%) elemental fluorine (F₂) innitrogen (N₂) as inert gas, and using a microreactor gave lowconversions to fluorinated products, but in very selective, cleanreactions. Nevertheless, also in this process described by Chambers,typically, reactions are carried out only in small scale reactions, forexample over a 16 h period enabling 5 to 10 g of crude product to becollected. Importantly, it must be noted that despite the successfulconversions in the range of 78% to 91% of fluorination reactions ondeactivated benzene derivatives with a diluted fluorination gas inacetonitrile as solvent, nevertheless Chambers did not test nor motivatefor testing of non-deactivated benzene itself, neither in small-scale of5 to 10 g product quantities nor in large-scale at all.

Accordingly, there is a high demand of enabling large-scale and/orindustrial production of fluorinated benzene involving a step of directfluorination in a controlled and effective manner in a large-scaleand/or industrial setting. Here, it is also an object of the inventionto provide a new process for enabling the manufacture or preparation ofbenzoic acid hypofluorite in a controlled and effective manner,preferably in a large-scale and/or industrial setting. Another object ofthe present invention is to provide the said benzoic acid hypofluoriteas a starting material for the manufacture or preparation of fluorinatedbenzene, preferably in a large-scale and/or industrial setting.

When producing fluorinated benzene in a two-step procedure by firstdirectly fluorinating benzoic acid in a controlled and effective manner,and then subsequently in the second step decarboxylating the benzoicacid hypofluorite obtained in the fluorination step, in another aspectit is also desired to minimize, or even to substantially avoid, thedilution of the elemental fluorine (F₂) by inert gas, e.g. by nitrogen(N₂) as inert gas, and at least to enable the use of fluorination gascontaining essentially higher concentrated elemental fluorine (F₂) thanthose concentrations described above and used in the prior art, e.g.,essentially higher concentrated elemental fluorine (F₂) than 10% byvolume as used by Chambers or available under exemption in Europe, oressentially higher concentrated elemental fluorine (F₂) than 20% byvolume as available in Asia.

It is an object of the present invention to provide a high efficientprocess for the manufacture or for preparation of a fluorinated benzene,in particular monofluorobenzene, involving a step of directfluorination, e.g., directly fluorinating benzoic acid, using fluorinegas (F₂), preferably wherein in the fluorination process a fluorine gas(fluorination gas) with concentrations of substantially more than, inparticular very much higher than 15 or even 20% by volume of elementalfluorine (F₂), especially of equal to much higher than 25% by volume(i.e., at least 25% by volume) of elemental fluorine (F₂), preferably ofequal to much higher than 35 or even 45% by volume of elemental fluorine(F₂), can be used for chemical synthesis, especially for the manufactureor for preparation of fluorobenzene compounds, in particularfluorobenzene (monofluorobenzene), as final products and/orintermediates, for usage in agro-, pharma-, electronics-, catalyst,solvent and other functional chemical applications.

It is preferably an object of the present invention to provide afluorination process for the manufacture or preparation of a fluorinatedbenzene, in particular monofluorobenzene, involving a step of directfluorination, e.g., directly fluorinating benzoic acid, using fluorinegas (F₂), by which it is possible to perform chemistry with afluorination gas consisting essentially of F₂-gas as it directly comesout of the F₂-electrolysis reactors (fluorine cells), optionally onlydiluted for a minor degree, e.g., for adapting and controlling thefluorination process and its parameters.

It is preferably another object of the present invention to provide afluorination process for the manufacture or preparation of a fluorinatedbenzene, in particular monofluorobenzene, involving a step of directfluorination, e.g., directly fluorinating benzoic acid, using fluorinegas (F₂-gas), by means of special equipment and special reactor design.

It is preferably still another object of the present invention toprovide a fluorination process for the manufacture or preparation of afluorinated benzene, in particular monofluorobenzene, involving a stepof direct fluorination, e.g., directly fluorinating benzoic acid, usingfluorine gas (F₂-gas), wherein the process can be performed in alarge-scale and/or industrial production of fluorinated benzene.

SUMMARY OF THE INVENTION

The objects of the invention are solved as defined in the claims, anddescribed herein after in detail.

The invention relates to a use of a fluorination gas, wherein theelemental fluorine (F₂) is preferably present in a high concentration,for example, in a concentration of elemental fluorine (F₂), especiallyof equal to much higher than 15% or even 20% by volume (i.e., at least15% or even 20% by volume), and to a process for the manufacture of afluorinated benzene starting from benzoic acid involving a step ofdirect fluorination employing a fluorination gas, wherein the elementalfluorine (F₂) is preferably present in a high concentration, andsubsequent decarboxylation of the benzoic acid hypofluorite obtained bydirect fluorination. The process of the invention is also directed tothe manufacture of a benzoic acid hypofluorite by direct fluorination ofbenzoic acid. Especially the invention is of interest in the preparationof benzoic acid hypofluorite, and/or subsequently fluorinated benzene,final products and as well intermediates, for usage in agro-, pharma-,electronics-, catalyst, solvent and other functional chemicalapplications. The fluorination process of the invention may be performedbatch-wise or in a continuous manner. If the process of the invention isperformed batch-wise, a column (tower) reactor may be used. If theprocess of the invention is continuous a microreactor may be used. Theinvention is characterized in that the starting compound is benzoicacid, and the fluorinated compound produced is a benzoic acidhypofluorite obtained by direct fluorination, which benzoic acidhypofluorite can be converted by decarboxylation to a fluorinatedbenzene, preferably monofluorobenzene.

The inventive process disclosed hereunder delivers fluorobenzene in highyield in environmental friendly and economic feasible manner involving astep of a direct fluorination of benzoic acid with F₂-gas to obtain thecorresponding benzoic acid hypofluorite (hypofluorusbenzoic acid)followed by a decarboxylation step to obtain a fluorinated benzene,preferably monofluorobenzene. The general two step reaction sequence isgiven hereunder.

The decarboxylation step to obtain a fluorinated benzene, preferablymonofluorobenzene, by decarboxylation of benzoic acid hypofluorite canbe performed by several options. For example, the decarboxylation may beperformed by thermal decarboxylation or photochemical decarboxylation.According to the invention a photochemical decarboxylation is preferred.A photochemical decarboxylation, for example, can be performed either bydirect irradiation (λ>180 nm, option 1), or in presence of aphotosensitizer also is also workable (light initiated, option 2).

A photochemical decarboxylation either by direct irradiation (λ>180nm=option 1) or in presence of a photosensitizer also is also workable(light initiated=option 2) and inventive, the reaction is induced bywavelength λ>180 nm (remark: but 254 nm is the strongest short wavelength line of a Hg-lamp), light can be produced by different lightsources like Hg-medium or Hg-high pressure lamps, Phillips tube lamps oreven LEDs. Pre-tests were made in a so called Rayonet PhotochemicalReactor RPR-100″ (supplier: “The Southern New England UltravioletCompany”) with 254 nm tubes. For industrial scale, immersed shaftphotolysis reactors are still the preferred ones as they use only 1Hg-lamp in the middle surrounded by product mixtures which have to beirradiated. LED reactors for reactions which need higher power areeconomically still less preferred as the construction of 1000s of coppercables into a system is necessary.

Advantage of a photochemical induced decarboxylation is the loweruseable temperature vs. the quite high temperature needed for thethermal decarboxylation. Photocatalyzed Decarboxylation and reactions ofcarboxylic acid hypobromide is described e.g. by Candish, L.; et al,Chemical Science (2017), 8(5), 3618-3622

(https://pubs.rsc.org/en/content/articlelanding/2017/SC/C6SC05533H#!divAbstract)but this procedure is not industrial suitable and not economic due tohigh cost of the photocatalyst and too low selectivities for thedescribed products.

Room Temperature

As traces of fluoride will already damage photoreactors made out ofglassware, any glassware and glass windows (e.g. if LEDs are used) needto be protected by a plastics coating, especially necessary forindustrial scale.

Some potential transparent plastics are, for example (see inhttps://www.interempresas.net/Plastico/Articulos/5544-La-transparencia-en-los-plasticos.html):

-   -   the ETFE, with a 95% light transmission    -   polimethyl methacrylate, with a rate of 92 percent;    -   the polystyrene, with an index equal to or greater than 90%;    -   the polycarbonate, ranging from 80% to 90%;    -   the cellulose, with rates of the order of 85 percent;    -   acrylo-styrene-butadiene, the amorphous polyamides, UP resins,        epoxys and phenolic and some other plastic f.

Optical Properties of Transparent Polymers

See, for example in:https://omnexus.specialchem.com/tech-library/article/comprehensive-list-of-transparent-polymers.

Transmission Refractive [%] Index Haze [%] PC 86-91 1.584-1.586 0.2-2.7PMMA 89-92 1.49 0.10-2.6  PET  87-92.1 1.575 0.20-5.1  PETG 92 1.55 0.7Clear PVC Upto 97% 1.381 2.5 LSR 94 1.41 <1 COC 91 1.53 3 LDPE 4.4-94 1.476  3-12 Ionomer Resin   93.4 1.49 2.7-4.2 Transparent PP — 1.347 —FEP 92 1.55 0.7 SMMA  89-92.8 1.59 0.3-1.0 SAN 86.2-89.3 1.57 0.4-2.8GPPS 88-90 1.6 0.3-1.1 Transparent ABS 86 1.52 3

Another source for transparent plastics:https://www.ultrapolymers.com/sites/default/files/421049-Transparent-Plastics-LR.pdf

The most suitable plastics is FEP or alternatively polycarbonate whichis used as a kind of shrinking pipe over the photoreactor or as a foiltype for covering glass windows. Fluorinated ethylene propylene (FEP) isa copolymer of hexafluoropropylene and tetrafluoroethylene. It differsfrom the polytetrafluoroethylene (PTFE) resins in that it ismelt-processable using conventional injection molding and screwextrusion techniques.

According to the objects, the present invention provides a highefficient process for the manufacture or for preparation of afluorinated benzene, in particular monofluorobenzene, involving a stepof direct fluorination using fluorine gas (F₂), e.g., a step offluorinating benzoic acid to obtain benzoic acid hypofluorite, whereinpreferably in the fluorination process a fluorine gas (fluorination gas)with concentrations of substantially more than, in particular very muchhigher than 15% by volume or in particular than 20% by volume ofelemental fluorine (F₂), especially of equal to much higher than 25% byvolume (i.e., at least 25% by volume) of elemental fluorine (F₂),preferably of equal to much higher than 35% by volume or in particularthan 45% by volume of elemental fluorine (F₂), is used for chemicalsynthesis, especially for the manufacture or for preparation of benzoicacid hypofluorite, and/or subsequently fluorinated benzene, inparticular monofluorobenzene, as final products and/or intermediates,for usage in agro-, pharma-, electronics-, catalyst, solvent and otherfunctional chemical applications.

Preferably, the present invention provides a fluorination process forthe manufacture or preparation of a fluorinated benzene, in particularmonofluorobenzene, involving a step of direct fluorination usingfluorine gas (F₂), e.g., a step of fluorinating benzoic acid to obtainbenzoic acid hypofluorite, by which it is possible to perform chemistrywith F₂ as it comes directly out of the F₂-electrolysis reactors(fluorine cells).

More preferably, the present invention provides a fluorination processfor the manufacture or preparation of a fluorinated benzene, inparticular monofluorobenzene, involving a step of direct fluorinationusing fluorine gas (F₂), e.g., a step of fluorinating benzoic acid toobtain benzoic acid hypofluorite, by means of special equipment andspecial reactor design, for example, as described in FIG. 1 and FIG. 2hereunder. The special equipment and special reactor design employed bythe invention may comprise one or more packed bed towers, e.g., in theform of a gas scrubber system, or one or more microreactors. A packedbed towers, e.g., in the form of a gas scrubber system, may bepreferred, more preferably a packed bed towers, e.g., in the form of aninverse gas scrubber system, used in a batch process as reactor.

The fluorination process for the manufacture or preparation of afluorinated benzene, in particular monofluorobenzene, involving a stepof direct fluorination using fluorine gas (F₂), e.g., a step offluorinating benzoic acid to obtain benzoic acid hypofluorite, can beperformed at suitable pressures, for examples at a pressure in the rangeof about 1 to about 10 bar (absolute), preferably at a pressure in arange of about 1 to about 6 bar (absolute), and more preferably at apressure in a range of about 4 to about 6 bar (absolute). In an example,the process is performed at a pressure of about 6 bar (absolute).

In the decarboxylation reaction, the pressure may, according to pressureconditions commonly used in in the technical field, and be in a range ofabout 1 to about 20 bar (absolute). For example, if the decarboxylationis carried out in an autoclave, the pressure can be 20 bar (absolute),and if the decarboxylation is carried out in a microreactor, pressurewill be in a range of about 1 bar (absolute) to 3 bar (absolute), forexample at a pressure of about 2 bar (absolute).

The fluorination process for the manufacture or preparation of afluorinated benzene, in particular monofluorobenzene, involving a stepof direct fluorination using fluorine gas (F₂), e.g., a step offluorinating benzoic acid to obtain benzoic acid hypofluorite, can beperformed at an approximately equimolar ratio of benzoic acid as thestarting compound to the fluorination gas comprising elemental fluorine(F₂), optionally of highly concentrated F₂-gas. Preferably, the reactionis performed with a slight molar excess amount of the fluorination gascomprising elemental fluorine (F₂), optionally of highly concentratedF₂-gas.

Further, it has been discovered that despite the exothermic character ofthe direct fluorination reaction, involving a step of directfluorination using fluorine gas (F₂), e.g., a step of fluorinatingbenzoic acid to obtain benzoic acid hypofluorite, e.g., within a giventime period (e.g., less than 10 hours, or even less than 5 hours), thereaction of the invention can be performed as a larger scale reactionwith high conversion rates, and without major impurities in theresulting fluorinated product. The fluorinated product can be producedin kilogram scale quantities, e.g., the direct fluorination process ofthe invention can be performed in a large-scale and/or industrialproduction of fluorinated benzene involving a step of directfluorination using fluorine gas (F₂), e.g., a step of fluorinatingbenzoic acid to obtain benzoic acid hypofluorite.

As a first reference for scale orientation, and for reason ofcalculating quantities, reference is made to the molecular weight ofbenzene of 78.114 g/mol, and of monofluorobenzene of 96.10 g/mol. Forreason of adapting and/or controlling process parameters, here theboiling point of benzene of about 80° C., and that of monofluorobenzeneof about 85° C. are also given, each for ambient pressure.

As a second reference for scale orientation, and for reason ofcalculating quantities, reference is made to the molecular weight ofbenzoic acid of 122.123 g/mol, and of benzoic acid hypofluorite of140.11 g/mol. For reason of adapting and/or controlling processparameters, here the melting point of about 122° C. and boiling point ofabout 250° C. of benzoic acid. Each of said ° C. value is for ambientpressure.

Accordingly, it is preferred that the direct fluorination process of theinvention is performed in a large-scale and/or industrial production offluorinated benzene (preferably monofluorobenzene), or of benzoic acidhypofluorite, respectively, involving a step of direct fluorinationusing fluorine gas (F₂), e.g., a step of fluorinating benzoic acid toobtain benzoic acid hypofluorite, e.g., in kilogram scale quantities,wherein in a batch process, or optionally in a continuous process, in acolumn reactor as described herein, at least about 1 kg of benzoic acidas the starting material is fluorinated per hour, preferably at leastabout 1.5 kg of benzoic acid as the starting material is fluorinated perhour, to yield benzoic acid hypofluorite, and/or subsequently afluorinated benzene, preferably monofluorobenzene, with a conversion ofat least 80%, in particular of at least 85%, preferably about at least90%, more preferably about at least 95% conversion.

Accordingly, it is preferred that the direct fluorination process of theinvention is performed in a large-scale and/or industrial production offluorinated benzene, or of benzoic acid hypofluorite, respectively,involving a step of direct fluorination using fluorine gas (F₂), e.g., astep of fluorinating benzoic acid to obtain benzoic acid hypofluorite,e.g., in a larger scale or even kilogram scale quantities, wherein in amicroreactor process, in a continuous process, as described herein, atleast about 0.5 mol/h benzoic acid (about 61 g/h benzoic acid), or atleast about 1 mol/h benzoic acid (about 122 g/h benzoic acid),preferably at least about 1.5 mol/h benzoic acid (about 183 g/h benzoicacid), more preferably at least about 2 mol/h or about 3 mol/h benzoicacid (about 244 g/h or about 366 g/h benzoic acid), as the startingmaterial is fluorinated for a desired period of time (e.g., of at least0.5 h, preferably of at least 1 h, more preferably of at least 2, 3, or4 h) to produce the required large-scale and/or industrial scalequantity of benzoic acid hypofluorite, and/or subsequently fluorinatedbenzene (preferably monofluorobenzene), with a conversion of at least80%, in particular of at least 85%, preferably about at least 90%, morepreferably about at least 95% conversion.

The reaction is performed with an equimolar amount of F₂-gas, optionallyof highly concentrated F₂-gas, as each defined herein, and preferably ina slight molar excess amount of about 0.1 to about 0.8 mol/h or of about0.1 to about 0.5 mol/h, preferably of about 0.1 to about 0.4 mol/h orabout 0.1 to about 0.3 mol/h, more preferably of about 0.1 to about 0.2mol/h, most preferably of about 0.15 mol/h, of F₂-gas, optionally ofhighly concentrated F₂-gas, as each defined herein.

In a particular embodiment, it is preferred that the direct fluorinationprocess of the invention is performed in a large-scale and/or industrialproduction of fluorinated benzene, or of benzoic acid hypofluorite,respectively, involving a step of direct fluorination using fluorine gas(F₂), e.g., a step of fluorinating benzoic acid to obtain benzoic acidhypofluorite, e.g., in kilogram scale quantities, wherein in amicroreactor process, in a continuous process, as described herein, atleast about 0.8 mol/h benzoic acid (about 100 g/h benzoic acid) as thestarting material is fluorinated for a desired period of time of atleast about 1 h or about 2 h or about 3 h or about 4 h, preferably of atleast about 4.5 h or 5 h, more preferably of at least about 6 h, about10 h, about 12 h or about 24 h, to produce the required large-scaleand/or industrial scale quantity of fluorinated benzene (preferablymonofluorobenzene), or of benzoic acid hypofluorite, respectively, witha conversion of at least 80%, in particular of at least 85%, preferablyabout at least 90%, more preferably about at least 95% conversion.Hence, in the said direct fluorination process of the inventionperformed in a large-scale and/or industrial production of fluorinatedbenzene (preferably monofluorobenzene), involving a step of directfluorination using fluorine gas (F₂), e.g., a step of fluorinatingbenzoic acid to obtain benzoic acid hypofluorite, in a microreactor in acontinuous process within the said time periods, e.g., whereinapproximate kilogram scale quantities of benzoic acid of at least about0.1 kg or about 0.2 kg or about 0.3 kg or about 0.4 kg or about 0.5 kg,or of at least about 1 kg, preferably of at least about 1.5 kg or about1.75 kg, more preferably of at least 2.0 kg, 2.5 kg, 3.5 kg or 5 kg, toproduce the required large-scale and/or industrial scale quantity offluorinated benzene (preferably monofluorobenzene), or of benzoic acidhypofluorite, respectively, with a conversion of at least 80%, inparticular of at least 85%, preferably about at least 90%, morepreferably about at least 95% conversion. The reaction is performed withan equimolar amount of F₂-gas, optionally of highly concentrated F₂-gas,and preferably in a molar amount of a slight excess of about 0.1 toabout 0.8 mol/h or of about 0.1 to about 0.5 mol/h, preferably of about0.1 to about 0.4 mol/h or about 0.1 to about 0.3 mol/h, more preferablyof about 0.1 to about 0.2 mol/h, most preferably of about 0.15 mol/h, ofF₂-gas, optionally of highly concentrated F₂-gas, as each definedherein.

The invention also relates to a use of a fluorination gas, preferablywherein elemental fluorine (F₂) is present in a high concentration ofsubstantially more than, in particular very much more than 15% by volumeor in particular than 20% by volume, preferably equal to or more than25% by volume (vol.-%), for the manufacture of a fluorinated benzene),or of benzoic acid hypofluorite, respectively, in a liquid mediumcomprising or consisting of benzoic acid as starting compound,preferably wherein the elemental fluorine (F₂) is present in thefluorine containing gas in a high concentration in a range of fromsubstantially more than, in particular very much more than 15 or 20 byvolume (vol.-%) and up to 100% by volume, preferably equal to or morethan 25 by volume (vol.-%) and up to 100% by volume (vol.-%);characterized in that the starting compound is benzoic acid, and thefluorinated compound produced is benzoic acid hypofluorite, and/orsubsequently a fluorinated benzene, preferably monofluorobenzene.

It is noted that the fluorination reaction of the present invention, inparticular when carried out in the specific and/or preferred equipmentor reactor designs as described by the present invention herein, can bealready performed with concentrations of elemental fluorine (F₂) of 15%by volume or in particular than 20% by volume.

However, it is preferred that the fluorination reaction of the presentinvention, also when carried out in the specific and/or preferredequipment or reactor designs as described by the present inventionherein, is performed with concentrations of elemental fluorine (F₂) atleast 25% by volume, and more preferably with concentrations ofelemental fluorine (F₂) of substantially more than 35% by volume or inparticular substantially more than 45% by volume of elemental fluorine(F₂).

According to the present invention it is particularly preferred toperform the fluorination process for the manufacture or preparation of afluorinated benzene, in particular monofluorobenzene, involving a stepof direct fluorination, e.g., a step of fluorinating benzoic acid toobtain benzoic acid hypofluorite, using fluorine gas (F₂), which comesdirectly out of the F₂-electrolysis reactors (fluorine cells). Suchelectrolysis fluorine gas (F₂) normally has a concentration of about 97%elemental fluorine (F₂).

The electrolysis fluorine gas (F₂) normally having a concentration ofabout 97% elemental fluorine (F₂) can be used without purification as itis derived from the F₂-electrolysis reactors (fluorine cells), or ifdesired, it may be purified.

Further, the electrolysis fluorine gas (F₂) normally having aconcentration of about 97% by volume (vol.-%) of elemental fluorine (F₂)can be used in the in the such concentration as it is derived from theF₂-electrolysis reactors (fluorine cells), or optionally it may bediluted by an inert gas, preferably nitrogen (N₂), to a desiredconcentration of at least 80% by volume (vol.-%) of elemental fluorine(F₂). More preferably the electrolysis fluorine gas (F₂) is onlydiluted, if desired, by no more than 15% by volume (vol.-%), no morethan 10% by volume (vol.-%), and most preferably by no more that 5% byvolume (vol.-%), of an inert gas, preferably nitrogen (N₂).

Surprisingly it was also found that the use of inert gas in largerratios of inert gas to elemental fluorine has disadvantages in terms ofprocess controllability of the fluorination reaction, for example, interms of effective mixing of the elemental fluorine with the liquidcompound to be fluorinated, heat transfer control, e.g., poor heatexchange, and maintenance of desired reaction conditions in themicro-environments in the reaction mixture. These disadvantages equallyapply in bed tower reactor (gas scrubber system) technology and inmicrobubble microreactor or comparable continuous flow technology. Forexample, in a coil reactor or microreactor, at high inert gasconcentrations, e.g., low fluorine (F₂) concentrations, in addition tothe poor heat exchange, there are also ineffective (reaction) zones with(inert) gas bubbles, which nullifies the advantages of using a coilreactor or a microreactor, and the same is observed in bed tower reactor(gas scrubber system) technology.

Definitions

Direct Fluorination: Introducing one or more fluorine atoms into acompound by chemically reacting a starting compound, e.g., according tothe present invention benzoic acid, with elemental fluorine (F₂) suchthat one or more fluorine atoms are covalently bound into thefluorinated product compound produced, which in case of the presentinvention is benzoic acid hypofluorite.

Compound: A molecule composed of at least two atoms bound by covalentbinding. In the molecule, often also called substance, the atoms arecovalently linked together to form a self-contained, chemical formation.A molecule defined in this way is the smallest particle of a certainpure substance and has a determinable molecular mass, wherein the atomsare held together by chemical bonds and are at least as long stable thatthey can be observed, for example, at least spectroscopically. Amolecule or substance defined in this way is the smallest part of acertain pure substance and has a determinable molecular mass, and otherdeterminable physiochemical properties. Here, in the invention, thestarting compound is benzoic acid provided to be reacted with elementalfluorine (F₂), and the compound produced, in a first step is benzoicacid hypofluorite, which in a second step is decarboxylated to yieldfluorobenzene, e.g., monofluorobenzene.

The term “liquid medium” may mean a solvent which inert to fluorinationunder the reaction conditions of the direct fluorination, in which thestarting compound and/or fluorinated target compound may be dissolved,and/or the starting compound itself may be a liquid serving itself asliquid medium, and in which the fluorinated target compound may bedissolved if it is not a liquid, or if it is a liquid may also serve asthe liquid medium.

In the present invention, if the starting compound or the resultingproduct compound is a solid, then the liquid medium is provided by meansof a solvent, especially, e.g. in case of a direct fluorination, thesolvent is at least more resistant to elemental fluorine (F₂) andhydrogen fluoride (HF) than the starting compound in the directfluorination reaction. A suitable (organic) solvent in the presentinvention, for example but not limiting, is acetonitrile. The directfluorination reaction, and/or the decarboxylation reaction, of thepresent invention can also be carried out in water, if the solidstarting compound is soluble in water (H₂O).

The numerical ranges disclosed herein include all values from, andincluding, the lower and upper value. For ranges containing explicitvalues (e.g., 1 to 7), any subrange between any two explicit values isincluded (e.g., 1 to 2; 2 to 6; 5 to 7; 3 to 7; 5 to 6; etc.).

The terms “comprising,” “including,” “having,” and their derivatives,are not intended to exclude the presence of any additional component,step or procedure, whether or not the same is specifically disclosed. Inorder to avoid any doubt, all compositions claimed through use of theterm “comprising” may include any additional additive, adjuvant, orcompound, whether polymeric or otherwise, unless stated to the contrary.In contrast, the term, “consisting essentially of” excludes from thescope of any succeeding recitation any other component, step, orprocedure, excepting those that are not essential to operability. Theterm “consisting of” excludes any component, step, or procedure notspecifically delineated or listed. The term “or,” unless statedotherwise, refers to the listed members individually as well as in anycombination. Use of the singular includes use of the plural and viceversa.

The term “vol.-%” as used herein means “% by volume”. Unless otherwisestated, all percentages (%) as used herein denote “vol.-%” or “% byvolume”, respectively.

For example, the use of the term “essentially”, in referring to afluorination gas consisting essentially of F₂-gas as it directly comesout of the F₂-electrolysis reactors (fluorine cells), means thatproviding such F₂-gas does not involve major purification and/orproviding another gas, e.g., an inert gas, separate and/or in admixturein amounts and/or under conditions that would be sufficient to provide achange in the composition of an F₂-gas as produced in and as it iswithdrawn as gaseous product from F₂-electrolysis reactors (fluorinecells) of more than about ±5% by volume, or preferably of more thanabout ±3% by volume. Accordingly, such a fluorination gas consistingessentially of F₂-gas as it directly comes out of the F₂-electrolysisreactors (fluorine cells) is meant to comprise elemental fluorine (F₂)in a concentration of at least about 92% by volume, or preferably of atleast about 95% by volume. Especially, such a fluorination gasconsisting essentially of F₂-gas as it directly comes out of theF₂-electrolysis reactors (fluorine cells) may comprise elementalfluorine (F₂) in a concentration in a range of about 92-100% by volume,or preferably in a range of about 95-100% by volume, or more preferablyin a range of in a range of about 92-99% by volume, or preferably in arange of about 95-99% by volume, or in a range of in a range of about 92to about 97% by volume, or preferably in a range of about 95 to about97% by volume.

Any pressure value or range of pressure values given herein in, i.e.,“bar”, unless otherwise stated refer to “bar absolute”.

The numerical ranges disclosed herein include all values from, andincluding, the lower and upper value. For ranges containing explicitvalues (e.g., 1 to 7), any subrange between any two explicit values isincluded (e.g., 1 to 2; 2 to 6; 5 to 7; 3 to 7; 5 to 6; etc.).

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows fluorination using a gas scrubber system.

FIG. 2 shows continuous fluorination in a one or several microreactor(in series) system.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

As briefly described in the Summary of the Invention, and defined in theclaims and further detailed by the following description and examplesherein, in a first reaction step, the invention is particularly makinguse of a fluorination gas, preferably wherein the elemental fluorine(F₂) is present in a high concentration, and to a process for themanufacture of a fluorinated benzene, preferably monofluorobenzene,involving a step of direct fluorination, e.g., a step of fluorinatingbenzoic acid to obtain benzoic acid hypofluorite, employing afluorination gas, preferably wherein the elemental fluorine (F₂) ispresent in a high concentration. Herein, the invention also relates to anew process for the manufacture or preparation of benzoic acidhypofluorite. Especially, this process for the manufacture orpreparation of benzoic acid hypofluorite may represent the firstreaction step in the process for the manufacture of a fluorinatedbenzene, preferably monofluorobenzene, wherein in said first reactionstep, benzoic acid is subjected to a direct fluorination employing afluorination gas, preferably, wherein the elemental fluorine (F₂) ispresent in a high concentration.

The invention makes use of a fluorination gas, preferably wherein theelemental fluorine (F₂) is present in a high concentration, for example,in a concentration of elemental fluorine (F₂) especially of equal tomuch higher than 15% or 20% by volume (i.e., at least 15% or 20% byvolume), and preferably at least 25% by volume, to a process for themanufacture of a fluorinated benzene, preferably monofluorobenzene,involving a step of direct fluorination using fluorine gas (F₂), e.g., astep of fluorinating benzoic acid to obtain benzoic acid hypofluorite,employing a fluorination gas, preferably wherein the elemental fluorine(F₂) is present in a high concentration. The process of the invention isdirected to the manufacture of a fluorinated benzene, preferablymonofluorobenzene, involving a step of direct fluorination usingfluorine gas (F₂), e.g., a step of fluorinating benzoic acid to obtainbenzoic acid hypofluorite, especially is of interest in the manufactureor preparation of fluorobenzene, in particular monofluorobenzene, asfinal products and as well intermediates, for usage in agro-, pharma-,electronics-, catalyst, solvent and other functional chemicalapplications. The fluorination process of the invention, e.g., the stepof fluorinating benzoic acid to obtain benzoic acid hypofluorite, may beperformed batch-wise or in a continuous manner. If the process of theinvention, e.g., the step of fluorinating benzoic acid to obtain benzoicacid hypofluorite, is performed batch-wise, a column (tower) reactor maybe used. If the process of the invention is continuous a microreactormay be used. If desired, it is also possible to perform the process ofthe invention continuously in a column (tower) reactor (gas scrubbersystem). However, it is preferred to perform a continuous process of theinvention, e.g., a step of fluorinating benzoic acid to obtain benzoicacid hypofluorite, in a microreactor.

Especially, in one aspect the invention is directed to the use of afluorination gas, preferably wherein elemental fluorine (F₂) is presentin a high concentration of substantially more than, in particular verymuch more than at least 10% by volume of elemental fluorine (F₂),especially of equal to much higher than 15% or 20% by volume (i.e., atleast 15% or 20% by volume), and preferably at least 25% by volume, forthe manufacture of benzoic acid hypofluorite, and/or subsequently afluorinated benzene, preferably monofluorobenzene, in a liquid mediumcomprising or consisting of benzoic acid as a starting compound,preferably wherein the fluorine (F₂) is present in the fluorinecontaining gas in a high concentration in a range of from substantiallymore than, in particular very much more than 15% or 20% by volume (i.e.,at least 15% or 20% by volume), and preferably at least 20% by volume,each up to 100% by volume, preferably equal to or more than 25% byvolume and up to 100% by volume (vol.-%).

In this invention it now was found that, preferably in special equipmentand with special reactor design such as, e.g., a microreactor or apacked bed tower (preferably made of Hastelloy), especially a packed bedtower containing fillers, e.g., metal fillers (e.g. Hastelloy) orplastic fillers, preferably wherein the tower (e.g., made out ofHastelloy) is filled either with E-TFE or metal fillings (Hastelloy),for example each of about 10 mm diameter as available from Raschig(http://www.raschig.de/Fllkrper). The type of fillings is quiteflexible, Raschigs Pall-Rings made out of Hastelloy can be used, andadvantageously E-TFE-fillings.

In the said special equipment and with special reactor design such as,e.g., a microreactor or a packed bed tower (preferably made ofHastelloy), a fluorine gas with concentrations of substantially morethan, in particular very much higher than 15% or 20% by volume ofelemental fluorine (F₂), especially of equal to much higher than 20% byvolume (i.e., at least 20% by volume) of elemental fluorine (F₂),preferably of equal to much higher than 25% by volume of elementalfluorine (F₂), can be used for chemical synthesis especially for thepreparation of benzoic acid hypofluorite, and/or subsequently afluorinated benzene (final products and/or intermediates) for usage inagro-, pharma-, electronics-, catalyst, solvent and other functionalchemical applications. This invention allows fluorination chemistry withF₂ gas with concentrations preferably equal to substantially more than,in particular very much higher than 25% by volume of elemental fluorine(F₂). In a applying the present fluorination process it is possible toperform chemistry with F₂ as it comes directly out of theF₂-electrolysis reactors (fluorine cells). A representative compositionof fluorine gas produced by a fluorine cell is 97% F₂, up to 3% CF₄(formed from damage of the electrodes), for example, traces of HF, NO₂,OF₂, COF₂, each % by volume and based on the total volume of thefluorine containing gas as 100% by volume.

Regarding the scope of the present invention it is to be noted that,that for legal reason only but not for technical reason, there is aproviso that the starting compound, to be reacted with the fluorinationgas, is only benzoic acid, and the fluorinated compound produced is onlybenzoic acid hypofluorite, and/or subsequently a fluorinated benzene,preferably the fluorinated benzene produced is only monofluorobenzene.

In the fluorination gas the elemental fluorine (F₂) may be diluted by aninert gas. The inert gas then constitutes the substantial difference(e.g., there may be only minor quantities of by-products (e.g., CF₄) ofno more than about 5% by volume, preferably of no more than about 3% byvolume, and only traces impurities (e.g., such like HF, NO₂, OF₂, COF₂),in the fluorination gas.

An inert gas is a gas that does not undergo chemical reactions under aset of given conditions. The noble gases often do not react with manysubstances and were historically referred to as the inert gases. Inertgases are used generally to avoid unwanted chemical reactions degradinga sample. These undesirable chemical reactions are often oxidation andhydrolysis reactions with the oxygen and moisture in air.

Typical inert gases are noble gases, and the very common inert gasnitrogen (N₂). The noble gases (historically also the inert gases;sometimes referred to as aerogens) make up a group of chemical elementswith similar properties; under standard conditions, they are allodorless, colorless, monatomic gases with very low chemical reactivity.The six noble gases that occur naturally are helium (He), neon (Ne),argon (Ar), krypton (Kr), xenon (Xe), and the radioactive radon (Rn).

Purified argon and nitrogen gases are most commonly used as inert gasesdue to their high natural abundance (78.3% N₂, 1% Ar in air) and lowrelative cost. The preferred is nitrogen (N₂) as the inert gas fordiluting the elemental fluorine (F₂) in the fluorination gas to thedesired but still high concentration, as defined herein.

Preferred is a fluorination gas, wherein the elemental fluorine (F₂) isdiluted by nitrogen (N₂). An example composition of a fluorination gas,using nitrogen (N₂) as the inert gas, is as follows (here as purifiedcomposition (fluorine-nitrogen gas mixture) as filled in a steel gascylinder):

Molecular Formula: F₂ Molecular Weight: 38 Item Index F₂ content (volume20 fraction)/10⁻² N₂ content (volume 80 fraction)/10⁻² O₂ content(volume ≤0.08 fraction)/10⁻² CF₄ content (volume ≤0.03 fraction)/10⁻² HFcontent (volume ≤0.50 fraction)/10⁻² Properties: melting point: −218°C., boiling point: −187° C., relative density (moisture = 1) 1.14 (−200°C.), soluble in water, relative density (air = 1) 1.70, saturated vaporpressure (kpa): 101.32 (−187° C.), critical pressure (MPA): 5.57.

The following two Figures (i.e. FIG. 1 and FIG. 2) illustrate theindustrial options to use F₂ gas with little or even with no dilutionwith inert gas:

FIG. 1: Fluorination using a gas scrubber system.

Batch fluorination with elemental fluorine (F₂) gas, optionally highlyconcentrated F₂ gas in a counter-current system (the reservoir iscontaining the liquid raw material or optionally the raw material in aninert solvent). If highly concentrated F₂ is used together with someinert gas (e.g. 10% N₂) the pressure during the fluorination is kept at5 bar (absolute) by a pressure valve. The inert gas together with (only)some HF leaves as purge gas during reaction.

FIG. 2: Continuous fluorination in a one or several microreactor (inseries) system.

The raw material reservoir still contains the equimolar formed HF. Thiscan be subjected a batch or continuous distillation or if a solvent ispresent, after removal of the solvent and HF a re-crystallization forpurification. Spray drying is another option depending on the productproperties. A second or even more microreactor in series is just for thepurpose of extending the residence time if needed.

Fluorination With Fluorination Gas Containing Elemental Fluorine in aHigh Concentration:

As shown in the examples, the direct fluorination using fluorine gas(F₂), e.g., in a step of fluorinating benzoic acid to obtain benzoicacid hypofluorite, can be performed already with a fluorination gas,based on the total fluorination gas composition as 100% by volume,comprising at least 20% by volume of elemental fluorine (F₂) and up toabout 80% by volume of an inert gas, preferably nitrogen (N₂), forexample, the composition of a fluorination gas, using nitrogen (N₂) asthe inert gas, as escribed above as purified compositionfluorine-nitrogen gas mixture as filled in a steel gas cylinder.

By the present invention it was found that the fluorination processaccording to the invention is already feasible with a fluorination gas,based on the total fluorination gas composition as 100% by volume,comprising at least 20% by volume of elemental fluorine (F₂), but for anindustrial process undesirably low conversion rates of only about up to30 to 45% are achieved.

Surprisingly it was also found that the use of inert gas in largerratios of inert gas to elemental fluorine has disadvantages in terms ofprocess controllability of the fluorination reaction, for example, interms of effective mixing of the elemental fluorine with the liquidcompound to be fluorinated, heat transfer control, e.g., poor heatexchange, and maintenance of desired reaction conditions in themicro-environments in the reaction mixture. These disadvantages equallyapply in bed tower reactor (gas scrubber system) technology and inmicrobubble microreactor or comparable continuous flow technology. Forexample, in a coil reactor or microreactor, at high inert gasconcentrations, e.g., low fluorine (F₂) concentrations, in addition tothe poor heat exchange, there are also ineffective (reaction) zones with(inert) gas bubbles, which nullifies the advantages of using a coilreactor or a microreactor, and the same is observed in bed tower reactor(gas scrubber system) technology.

However, it was also found by the present invention that, based on thetotal fluorination gas composition as 100% by volume, increasing theconcentration of elemental fluorine (F₂) in the fluorination gas to ahigher concentration of greater than 20% by volume, e.g., preferably ofgreater than 25% by volume, more preferably of greater than 30% byvolume or 40% by volume, and most preferably of greater than 50% byvolume, while on the other hand decreasing the concentration of theinert gas, e.g., of the inert gas nitrogen (N₂), to a correspondinglower concentration of less than 80% by volume, e.g., preferably of lessthan 75% by volume, more preferably of less than 70% by volume or 60% byvolume, and most preferably of less than 50% by volume, for anindustrial process gradually increasing conversion rates of essentiallyabove about 30 to 45%, e.g. conversion rates of more than 50% by volume,preferably of more than 60% by volume, or more than 70% by volume, ormore than 70% by volume, even more preferably of more than 80% byvolume, and most preferably of more than 90% by volume, can be achieved.

Without wishing to be bound to a theory, it is estimated that the inertgas used to dilute the reactivity of the strongly oxidant elementalfluorine (F₂), which is required for safety reasons when handling andtransporting elemental fluorine (F₂) as described in the backgroundabove (e.g., in Europe mixtures of 95% by volume N2 (inert gas) withonly 5% by volume F₂-gas, or in Asia, e.g., at least 80% by volume N2(inert gas) with only up to 20% by volume F₂-gas) is jeopardizing thefluorination reaction, despite the fact that the elemental fluorine (F₂)contained in such a diluted fluorination gas still is strong oxidant.

Surprisingly, by the present invention it was found, that directfluorination of compounds, a direct fluorination using fluorine gas(F₂), e.g., in a step of fluorinating benzoic acid to obtain benzoicacid hypofluorite, with even higher conversion rates than those obtainedwith the said conventional diluted fluorination gases can be achieved,if the elemental fluorine (F₂) is undiluted by inert gas, or elementalfluorine (F₂) is diluted by inert gas only to a concentration of greaterthan 50% by volume elemental fluorine (F₂) in the fluorination gas,based on the total fluorination gas composition as 100% by volume.

Therefore, it is particularly preferred by the present invention toprovide a fluorination process for the manufacture or preparation offluorobenzene, in particular monofluorobenzene, involving a step ofdirect fluorination, e.g., a step of fluorinating benzoic acid to obtainbenzoic acid hypofluorite, using fluorine gas (F₂) as it comes directlyout of a F₂-electrolysis reactor (fluorine cell).

A representative composition of fluorine gas produced by a fluorine cellis 97% F₂, up to 3% CF₄ (formed from damage of the electrodes), tracesof HF, NO₂, OF₂, COF₂, each % by volume and based on the total volume ofthe fluorine containing gas as 100% by volume.

Purification of the fluorination gas as it is derived from aF₂-electrolysis reactor (fluorine cell), if desired, optionally ispossible, to remove a part or all by-products and traces formed in theF₂-electrolysis reactor (fluorine cell), prior to its use asfluorination gas in the process of the present invention. However, inthe process of the present invention such a partial or completepurification is not required, and the fluorination gas can be directlyused, as it comes directly out of a F₂-electrolysis reactor (fluorinecell).

When employing a fluorination gas derived from a F₂-electrolysis reactor(fluorine cell), purified or unpurified, it may, if desired, optionallybe diluted to some extent by an inert gas, preferably by nitrogen (N₂).

Hence, such a fluorination gas, purified or unpurified, as it is derivedfrom a F₂-electrolysis reactor (fluorine cell), if desired, mayoptionally be diluted by up to about 45% by volume of inert gas, butpreferably the fluorination gas is not diluted by inert gas to aconcentration of elemental fluorine (F₂) in the fluorination gas of less80% by volume, preferably of less than 85% by volume, more preferably ofless than 90% by volume, based on the total fluorination gas compositionas 100% by volume.

The difference of the sum of the elemental fluorine (F₂) and any inertgas in the fluorination gas to 100% by volume, if any difference, may beconstituted by by-products (e.g., CF₄) and traces of HF, NO₂, OF₂, COF₂,formed from damage of the electrodes of the F₂-electrolysis reactor(fluorine cell). This applies generally to the % by volume values givenherein above and herein below, if fluorine gas (F₂), as it comesdirectly out of a F₂-electrolysis reactor (fluorine cell) is used as thefluorination gas in the present invention.

Accordingly, in a preferred process of the invention the directfluorination, e.g., the step of fluorinating benzoic acid to obtainbenzoic acid hypofluorite, is carried out with a fluorination gascomprising about 80% by volume to 97±1% of elemental fluorine (F₂) andabout 0% to 17±1% of inert gas, preferably of nitrogen (N₂), based onthe total fluorination gas composition as 100% by volume.

In a further preferred process of the invention the direct fluorination,e.g., the step of fluorinating benzoic acid to obtain benzoic acidhypofluorite, is carried out with a fluorination gas comprising about85% by volume to 97±1% of elemental fluorine (F₂) and about 0% to 12±1%of inert gas, preferably of nitrogen (N₂), based on the totalfluorination gas composition as 100% by volume.

In a furthermore preferred process of the invention the directfluorination, e.g., the step of fluorinating benzoic acid to obtainbenzoic acid hypofluorite, is carried out with a fluorination gascomprising about 87% by volume to 97±1% of elemental fluorine (F₂) andabout 0% to 10±1% of inert gas, preferably of nitrogen (N₂), based onthe total fluorination gas composition as 100% by volume.

In another preferred process of the invention the direct fluorination,e.g., the step of fluorinating benzoic acid to obtain benzoic acidhypofluorite, is carried out with a fluorination gas comprising about90% by volume to 97±1% of elemental fluorine (F₂) and about 0% to 7±1%of inert gas, preferably of nitrogen (N₂), based on the totalfluorination gas composition as 100% by volume.

In still another preferred process of the invention the directfluorination, e.g., the step of fluorinating benzoic acid to obtainbenzoic acid hypofluorite, is carried out with a fluorination gascomprising about 95% by volume to 97±1% of elemental fluorine (F₂) andabout 0% to 2±1% of inert gas, preferably of nitrogen (N₂), based on thetotal fluorination gas composition as 100% by volume.

It goes without saying that a person skilled in the art understands thatwithin any of the given ranges any intermediate values and intermediateranges can be selected, too.

Use of Fluorination Gas With High Concentration of Elemental Fluorine:

The invention also relates to a use of a fluorination gas, preferablywherein elemental fluorine (F₂) is present in a high concentration ofsubstantially more than, in particular very much more than 15% by volumeor in particular than 20% by volume of elemental fluorine (F₂),especially of equal to much higher than 25% by volume, i.e., at least25% by volume, of elemental fluorine (F₂), preferably of equal to muchhigher than 35% by volume or in particular than 45% by volume, for themanufacture of benzoic acid hypofluorite, and/or subsequently afluorinated benzene in a liquid medium comprising or consisting of abenzoic acid as starting compound, characterized in that the startingcompound is benzoic acid, and the fluorinated compound produced isbenzoic acid hypofluorite, and/or subsequently a fluorinated benzene,preferably monofluorobenzene.

In general, in one aspect the invention is also directed to the use of afluorination gas, preferably wherein the elemental fluorine (F₂) ispresent in a high concentration, e.g., a use in a process for themanufacture of benzoic acid hypofluorite, and/or subsequently afluorinated benzene according to the invention, wherein the elementalfluorine (F₂) is present in the fluorination gas in a high concentrationof at least 25% by volume, preferably of at least 30% by volume, morepreferably of at least 35% by volume, even more preferably of at least45% by volume, each based on the total volume of the fluorination gas as100% by volume.

Furthermore, in the said use, the elemental fluorine (F₂) can be presentin the fluorination gas in a high concentration of at least 45% byvolume, preferably of at least 50% by volume, more preferably of atleast 60% by volume, even more preferably of at least 70% by volume, orof at least 80% by volume, each based on the total volume of thefluorination gas as 100% by volume.

In the said use for the manufacture of benzoic acid hypofluorite, and/orsubsequently a fluorinated benzene, preferably monofluorobenzene,according to the invention, in an embodiment the elemental fluorine (F₂)is present in the fluorination gas in a high concentration within arange of from 15-100% by volume, preferably within a range of from20-100% by volume, more preferably within a range of from 25-100% byvolume, still more preferably within a range of from 30-100% by volume,even more preferably within a range of from 35-100% by volume, an stillmore preferred within a range of from 45-100% by volume, each based onthe total volume of the fluorination gas as 100% by volume.

Furthermore, in the said use, the elemental fluorine (F₂) can be presentin the fluorination gas in a high concentration within a range of from45-100% by volume, preferably within a range of from 50-100% by volume,more preferably within a range of from 60-100% by volume, still morepreferably within a range of from 70-100% by volume, even morepreferably within a range of from 80-100% by volume, each based on thetotal volume of the fluorination gas as 100% by volume.

The Process of the Invention:

As briefly described in the Summary of the Invention, and defined in theclaims and further detailed by the following description and examplesherein, the invention is particularly directed to a process for themanufacture of benzoic acid hypofluorite, and/or subsequently afluorinated benzene, involving a step of direct fluorination, e.g., astep of fluorinating benzoic acid to obtain benzoic acid hypofluorite,wherein the process comprises the steps of direct fluorination anddecarboxlation as described herein after.

An embodiment of the invention relates to a process for the manufactureof a fluorinated benzene, preferably monofluorobenzene, wherein theprocess comprises the steps of:

-   -   a) provision of a liquid medium comprising benzoic acid as        starting compound;    -   b) provision of a fluorination gas comprising or consisting of        elemental fluorine (F₂), preferably wherein the fluorine is        present in the fluorination gas in a high concentration of at        least substantially more than, in particular very much more than        15% by volume (vol.-%), preferably equal to or more than 20% by        volume (vol.-%);    -   c) provision of a first reactor or reactor system, resistant to        elemental fluorine (F₂) and hydrogen fluoride (HF);    -   d) in a step of direct fluorination, passing the fluorination        gas of b), in a reactor or reactor system of c), through the        liquid medium of a) comprising the benzoic acid as starting        compound, and thereby reacting the benzoic acid starting        compound with the elemental fluorine (F₂) of the fluorination        gas a) to substitute in the hydrogen atom in the benzoic acid        carboxlylic group for fluorine, and wherein the reaction is        carried out at temperature of from about −30° C. to about        +100° C. and a pressure of from about 1 bar absolute bar to        about 10 bar absolute bar;    -   e) withdrawing the benzoic acid hypofluorite formed in the        direct fluorination step d) from the reactor or reactor system        of c);    -   f) to obtain the benzoic acid hypofluorite, in situ or in        isolated form; and    -   g) subjecting the benzoic acid hypofluorite obtained in step f),        in situ or in isolated form, in a second reactor or reactor        system to decarboxylation, to thereby obtain the fluorinated        benzene, preferably to obtain monofluorobenzene.

In the said process for the manufacture of benzoic acid hypofluorite,and/or subsequently a fluorinated benzene, preferably monofluorobenzene,according to the invention, in an embodiment the elemental fluorine (F₂)is present in the fluorination gas of b) in a high concentration of atleast 25% by volume, preferably of at least 30% by volume, morepreferably of at least 35% by volume, even more preferably of at least45% by volume, each based on the total volume of the fluorination gas as100% by volume.

In the said process for the manufacture of benzoic acid hypofluorite,and/or subsequently a fluorinated benzene, preferably monofluorobenzene,according to the invention, in an embodiment the fluorine (F₂) ispresent in the fluorination gas of b) in a high concentration within arange of from 15-100% by volume, preferably within a range of from20-100% by volume, more preferably within a range of from 25-100% byvolume, still more preferably within a range of from 30-100% by volume,even more preferably within a range of from 35-100% by volume, an stillmore preferred within a range of from 45-100% by volume, each based onthe total volume of the fluorination gas as 100% by volume.

Batch Process:

The invention also may pertain to a process for the manufacture ofbenzoic acid hypofluorite, and/or subsequently a fluorinated benzene,preferably monofluorobenzene, wherein the process is a batchwiseprocess, preferably wherein the batchwise process is carried out in acolumn reactor. Although, in the following reactor setting the processis described as a batch process, as preferred, for example, in case ofhigh product concentrations, optionally the process can be performed inthe said reactor setting also as a continuous process. In case of acontinuous process in the said reactor setting, then, it goes withoutsaying, the additional inlet(s) and outlet(s) are foreseen, for feedingthe starting compound and withdrawing the product compound,respectively.

If the invention pertains to a batchwise process, preferably wherein thebatchwise process is carried out in a column reactor, the process forthe manufacture of benzoic acid hypofluorite, and/or subsequently afluorinated benzene, preferably monofluorobenzene, according, mostpreferably the reaction is carried out in a (closed) column reactor(system), wherein the liquid medium of a) comprising or consisting ofthe starting compound benzoic acid is circulated in a loop, while thefluorination gas of b) comprising or consisting of elemental fluorine(F₂), optionally elemental fluorine (F₂) in a high concentration, is fedinto the column reactor, and c) is passed through the liquid medium toreact with the starting compound benzoic acid; preferably wherein theloop is operated with a circulation velocity of from about 1,500 l/h toabout 5,000 l/h, more preferably of from about 3,500 l/h to about 4,500l/h. In an example, the loop is operated with a circulation velocity ofabout 4,000 l/h.

If the invention pertains to a batchwise process, the process for themanufacture of benzoic acid hypofluorite, and/or subsequently afluorinated benzene, preferably monofluorobenzene, according to theinvention can be carried out such that the liquid medium of a)comprising or consisting of the starting compound benzoic acid iscirculated in the column reactor in a turbulent stream or in laminarstream, preferably in a turbulent stream.

In general, the fluorination gas containing the elemental fluorine (F₂)is fed into the loop in accordance with the required stoichiometry forthe targeted fluorinated product and fluorination degree, and adapted tothe reaction rate.

The said process for the manufacture of benzoic acid hypofluorite,and/or subsequently a fluorinated benzene, preferably monofluorobenzene,according to the invention, may be performed, e.g., batchwise, whereinthe column reactor is equipped with at least one of the following: atleast one cooler (system), at least one liquid reservoir for the liquidmedium of a) comprising or consisting of a starting compound benzoicacid, a pump (for pumping/circulating the liquid medium), one or more(nozzle) jets, preferably placed at the top of the column reactor, forspraying the circulating medium into the column reactor, one or morefeeding inlets for introducing the fluorination gas of b) comprising orconsisting of elemental fluorine (F₂), optionally elemental fluorine(F₂) in a high concentration, optionally one or more sieves, preferablytwo sieves, preferably the one or more sieves placed at the bottom ofthe column reactor, at least one gas outlet equipped with a pressurevalve.

The pressure valve functions to keep the pressure, as required in thereaction, and to release any effluent gas, e.g. inert carrier gascontained in the fluorination gas, if applicable together with anyhydrogen fluoride (HF) released from the reaction.

The said process for the manufacture of benzoic acid hypofluorite,and/or subsequently a fluorinated benzene, preferably monofluorobenzene,according to the invention, may be performed, e.g., batchwise, such thatin the said process for the manufacture of benzoic acid hypofluorite,and/or subsequently a fluorinated benzene, preferably monofluorobenzene,the column reactor is a packed bed tower reactor, preferably a packedbed tower reactor which is packed with metal fillers.

The packed tower according to FIG. 1 can have a diameter of, e.g., 100or 200 mm (depending on the circulating flow rate and scale) made out ofhigh grade stainless steel (1.4571) and a length of, e.g., 3 meters forthe 100 mm and, e.g., a length of 6 meters for the 200 mm diameter tower(latter if higher capacities are needed). The tower made out ofHastelloy is filled either with E-TFE or metal fillings each of, e.g.,10 mm diameter as available from Raschig(http://www.raschig.de/Fllkrper). The type of fillings is quiteflexible, Raschigs Pall-Rings made out of Hastelloy were used in thetrials disclosed hereunder, also E-TFE-fillings showed same performance,both not causing too much pressure reduction (pressure loss) whilefeeding F₂-gas in counter-current manner.

In the process for the manufacture of benzoic acid hypofluorite, and/orsubsequently a fluorinated benzene, preferably monofluorobenzene,according to any of the embodiments of the invention, the reaction maybe carried out with a counter-current flow of circulating liquid mediumof a) comprising or consisting of the starting compound benzoic acid andthe fluorination gas of b) fed into the column reactor and comprising orconsisting of elemental fluorine (F₂), optionally elemental fluorine(F₂) in a high concentration.

Here, the invention comprises, for example, the following embodiments.

In one embodiment, a process for the manufacture of benzoic acidhypofluorite, and/or subsequently a fluorinated benzene according to theinvention, wherein the reaction in step d) is carried out in a (closed)column reactor, wherein the liquid medium of a) comprising or consistingof the benzoic acid as the starting compound is circulated in a loop,while the fluorination gas of b) comprising or consisting of elementalfluorine (F₂), optionally elemental fluorine (F₂) in a highconcentration, is fed into the column reactor of c) and in step d) ispassed through the liquid medium to react with the starting compoundbenzoic acid; preferably wherein the loop is operated with a circulationvelocity of from 1,500 l/h to 5,000 l/h, more preferably of from 3,500l/h to 4,500 l/h.

In further embodiment, a process for the manufacture of benzoic acidhypofluorite, and/or subsequently a fluorinated benzene according to theinvention, wherein the column reactor is equipped with at least one ofthe following:

-   -   (i) at least one cooler (system), at least one liquid reservoir,        with inlet and outlet for, and containing the liquid medium        of a) comprising or consisting of benzoic acid as the starting        compound;    -   (ii) a pump for pumping and circulating the liquid medium of a);    -   (iii) one or more (nozzle) jets, preferably wherein the one or        more (nozzle) jets are placed at the top of the column reactor,        for spraying the circulating medium of a) into the column        reactor;    -   (iv) one or more feeding inlets for introducing the fluorination        gas of b) comprising or consisting of elemental fluorine (F₂),        optionally elemental fluorine (F₂) in a high concentration, into        the column reactor;    -   (v) optionally one or more sieves, preferably two sieves,        preferably the one or more sieves placed at the bottom of the        column reactor;    -   (vi) and at least one gas outlet equipped with a pressure valve,        and at least one outlet for withdrawing the benzoic acid        hypofluorite, for in situ or in isolated form, in step e).

In another embodiment, a process for the manufacture of benzoic acidhypofluorite, and/or subsequently a fluorinated benzene according to theinvention, wherein column reactor is a packed bed tower reactor,preferably a packed bed tower reactor which is packed with fillersresistant to elemental fluorine (F₂) and hydrogen fluoride (HF), e.g.with Raschig fillers and/or metal fillers, more preferably wherein thepacked bed tower reactor is a gas scrubber system (tower) which ispacked with fillers resistant to elemental fluorine (F₂) and hydrogenfluoride (HF), e.g. Raschig fillers and/or metal fillers.

In still another embodiment, process for the manufacture of benzoic acidhypofluorite, and/or subsequently a fluorinated benzene according to theinvention, wherein the reaction is carried out with a counter-currentflow of the circulating liquid medium of a) comprising or consisting ofthe benzoic acid as starting compound and of the fluorination gas of b)fed into the column reactor and which fluorination gas of b) iscomprising or consisting of elemental fluorine (F₂), optionallyelemental fluorine (F₂) in a high concentration.

The batch process in the tower column described above, can also beperformed, if desired, in a continuous manner. The person skilled in thefield, e.g. in chemical engineering knows about appropriate means andits arrangement necessary to continuously feed in new starting compoundand fluorination gas in the required amounts in a certain reaction timeperiod to compensate for the starting compound converted into thefluorinated compound, which fluorinated compound is withdrawn from thereaction in a certain time period when performing the reactioncontinuously.

Microreactor Process:

The invention also may pertain to a process for the manufacture ofbenzoic acid hypofluorite, and/or subsequently a fluorinated benzene,preferably monofluorobenzene, according to any of the preceding claims,wherein the process is a continuous process, preferably wherein thecontinuous process is carried out in a microreactor.

In general, the fluorination gas containing the elemental fluorine (F₂)is fed into the microreactor in accordance with the requiredstoichiometry (sometimes with a slight excess) for the targetedfluorinated product and fluorination degree, and adapted to the reactionrate.

The invention may employ more than a single microreactor, i.e., theinvention may employ two, three, four, five or more microreactors, foreither extending the capacity or residence time, for example, to up toten microreactors in parallel or four microreactors in series. If morethan a single microreactor is employed, then the plurality ofmicroreactors can be arranged either sequentially or in parallel, and ifthree or more microreactors are employed, these may be arrangedsequentially, in parallel or both. See FIG. 2.

The invention is also very advantageous, in one embodiment wherein thedirect fluorination of the invention, e.g., the step of fluorinatingbenzoic acid to obtain benzoic acid hypofluorite, optionally isperformed in a continuous flow reactor system, or preferably in amicroreactor system.

In an preferred embodiment the invention relates to a process for themanufacture of a fluorinated compound according to the invention,wherein the reaction is carried out in at least one step as a continuousprocesses, wherein the continuous process is performed in at least onecontinuous flow reactor with upper lateral dimensions of about ≤5 mm, orof about ≤4 mm,

preferably in at least one microreactor;

more preferably wherein of the said steps at least the step of afluorination reaction is a continuous process in at least onemicroreactor under one or more of the following conditions:

-   -   flow rate: of from about 10 ml/h up to about 400 l/h;    -   temperature: of from about 30° C. up to about 150° C.;    -   pressure: of from about 4 bar up to about 50 bar;    -   residence time: of from about 1 second, preferably from about 1        minute, up to about 60 minutes.

In another preferred embodiment the invention relates to such a processof preparing a compound according to the invention, wherein at least oneof the said continuous flow reactors, preferably at least one of themicroreactors, independently is a SiC-continuous flow reactor,preferably independently is a SiC-microreactor.

The Continuous Flow Reactors and Microreactors:

In addition to the above, according to one aspect of the invention, alsoa plant engineering invention is provided, as used in the processinvention and described herein, pertaining to the optional, and in someembodiments of the process invention, the process even preferredimplementation in microreactors.

As to the term “microreactor”: A “microreactor” or “microstructuredreactor” or “microchannel reactor”, in one embodiment of the invention,is a device in which chemical reactions take place in a confinement withtypical lateral dimensions of about ≤1 mm; an example of a typical formof such confinement are microchannels. Generally, in the context of theinvention, the term “microreactor”: A “microreactor” or “microstructuredreactor” or “microchannel reactor”, denotes a device in which chemicalreactions take place in a confinement with typical lateral dimensions ofabout ≤5 mm.

Microreactors are studied in the field of micro process engineering,together with other devices (such as micro heat exchangers) in whichphysical processes occur. The microreactor is usually a continuous flowreactor (contrast with/to a batch reactor). Microreactors offer manyadvantages over conventional scale reactors, including vast improvementsin energy efficiency, reaction speed and yield, safety, reliability,scalability, on-site/on-demand production, and a much finer degree ofprocess control.

Microreactors are used in “flow chemistry” to perform chemicalreactions.

In flow chemistry, wherein often microreactors are used, a chemicalreaction is run in a continuously flowing stream rather than in batchproduction. Batch production is a technique used in manufacturing, inwhich the object in question is created stage by stage over a series ofworkstations, and different batches of products are made. Together withjob production (one-off production) and mass production (flow productionor continuous production) it is one of the three main productionmethods. In contrast, in flow chemistry the chemical reaction is run ina continuously flowing stream, wherein pumps move fluid into a tube, andwhere tubes join one another, the fluids contact one another. If thesefluids are reactive, a reaction takes place. Flow chemistry is awell-established technique for use at a large scale when manufacturinglarge quantities of a given material. However, the term has only beencoined recently for its application on a laboratory scale.

Continuous flow reactors, e.g. such as used as microreactor, aretypically tube like and manufactured from non-reactive materials, suchknown in the prior art and depending on the specific purpose and natureof possibly aggressive agents and/or reactants. Mixing methods includediffusion alone, e.g. if the diameter of the reactor is narrow, e.g. <1mm, such as in microreactors, and static mixers. Continuous flowreactors allow good control over reaction conditions including heattransfer, time and mixing. The residence time of the reagents in thereactor, i.e. the amount of time that the reaction is heated or cooled,is calculated from the volume of the reactor and the flow rate throughit: Residence time=Reactor Volume/Flow Rate. Therefore, to achieve alonger residence time, reagents can be pumped more slowly, just a largervolume reactor can be used and/or even several microreactors can beplaced in series, optionally just having some cylinders in between forincreasing residence time if necessary for completion of reaction steps.In this later case, cyclones after each microreactor help to let escapeany gas formed during reaction, e.g. HF formed in the in the (first)fluorination step HF or CO₂ formed in the (second) decarboxylation step,and to positively influence the reaction performance. Production ratescan vary from milliliters per minute to liters per hour.

Some examples of flow reactors are spinning disk reactors (ColinRamshaw); spinning tube reactors; multi-cell flow reactors; oscillatoryflow reactors; microreactors; hex reactors; and aspirator reactors. Inan aspirator reactor a pump propels one reagent, which causes a reactantto be sucked in. Also to be mentioned are plug flow reactors and tubularflow reactors.

In the present invention, in one embodiment it is particularly preferredto employ a microreactor.

In the use and processes according to the invention in a preferredembodiment the invention is using a microreactor. But it is to be notedin a more general embodiment of the invention, apart from the saidpreferred embodiment of the invention that is using a microreactor, anyother, e.g. preferentially pipe-like, continuous flow reactor with upperlateral dimensions of up to about 1 cm, and as defined herein, can beemployed. Thus, such a continuous flow reactor preferably with upperlateral dimensions of up to about ≤5 mm, or of about ≤4 mm, refers to apreferred embodiment of the invention, e.g. preferably to amicroreactor. Continuously operated series of STRs is another option,but less preferred than using a microreactor.

In the before said embodiments of the invention, the minimal lateraldimensions of the, e.g. preferentially pipe-like, continuous flowreactor can be about >5 mm; but is usually not exceeding about 1 cm.Thus, the lateral dimensions of the, e.g. preferentially pipe-like,continuous flow reactor can be in the range of from about >5 mm up toabout 1 cm, and can be of any value therein between. For example, thelateral dimensions of the, e.g. preferentially pipe-like, continuousflow reactor can be about 5.1 mm, about 5.5 mm, about 6 mm, about 6.5mm, about 7 mm, about 7.5 mm, about 8 mm, about 8.5 mm, about 9 mm,about 9.5 mm, and about 10 mm, or can be can be of any valueintermediate between the said values.

In the before said embodiments of the invention using a microreactorpreferentially the minimal lateral dimensions of the microreactor can beat least about 0.25 mm, and preferably at least about 0.5 mm; but themaximum lateral dimensions of the microreactor does not exceed about ≤5mm. Thus, the lateral dimensions of the, e.g. preferential microreactorcan be in the range of from about 0.25 mm up to about ≤5 mm, andpreferably from about 0.5 mm up to about ≤5 mm, and can be of any valuetherein between. For example, the lateral dimensions of the preferentialmicroreactor can be about 0.25 mm, about 0.3 mm, about 0.35 mm, about0.4 mm, about 0.45 mm, and about 5 mm, or can be of any valueintermediate between the said values.

As stated here before in the embodiments of the invention in itsbroadest meaning is employing, preferentially pipe-like, continuous flowreactor with upper lateral dimensions of up to about 1 cm. Suchcontinuous flow reactor, for example is a plug flow reactor (PFR).

The plug flow reactor (PFR), sometimes called continuous tubularreactor, CTR, or piston flow reactors, is a reactor used to perform anddescribe chemical reactions in continuous, flowing systems ofcylindrical geometry. The PFR reactor model is used to predict thebehavior of chemical reactors of such design, so that key reactorvariables, such as the dimensions of the reactor, can be estimated.

Fluid going through a PFR may be modeled as flowing through the reactoras a series of infinitely thin coherent “plugs”, each with a uniformcomposition, traveling in the axial direction of the reactor, with eachplug having a different composition from the ones before and after it.The key assumption is that as a plug flows through a PFR, the fluid isperfectly mixed in the radial direction (i.e. in the lateral direction)but not in the axial direction (forwards or backwards).

Accordingly, the terms used herein to define the reactor type used inthe context of the invention such like “continuous flow reactor”, “plugflow reactor”, “tubular reactor”, “continuous flow reactor system”,“plug flow reactor system”, “tubular reactor system”, “continuous flowsystem”, “plug flow system”, “tubular system” are synonymous to eachother and interchangeably by each other.

The reactor or system may be arranged as a multitude of tubes, which maybe, for example, linear, looped, meandering, circled, coiled, orcombinations thereof. If coiled, for example, then the reactor or systemis also called “coiled reactor” or “coiled system”.

In the radial direction, i.e. in the lateral direction, such reactor orsystem may have an inner diameter or an inner cross-section dimension(i.e. radial dimension or lateral dimension, respectively) of up toabout 1 cm. Thus, in an embodiment the lateral dimension of the reactoror system may be in the range of from about 0.25 mm up to about 1 cm,preferably of from about 0.5 mm up to about 1 cm, and more preferably offrom about 1 mm up to about 1 cm.

In further embodiments the lateral dimension of the reactor or systemmay be in the range of from about >5 mm to about 1 cm, or of from about5.1 mm to about 1 cm.

If the lateral dimension at maximum of up to about ≤5 mm, or of up toabout ≤4 mm, then the reactor is called “microreactor”. Thus, in stillfurther microreactor embodiments the lateral dimension of the reactor orsystem may be in the range of from about 0.25 mm up to about ≤5 mm,preferably of from about 0.5 mm up to about ≤5 mm, and more preferablyof from about 1 mm up to about ≤5 mm; or the lateral dimension of thereactor or system may be in the range of from about 0.25 mm up to about≤4 mm, preferably of from about 0.5 mm up to about ≤4 mm, and morepreferably of from about 1 mm up to about ≤4 mm.

In case reactants are solid inert solvents may be used. Thus, if rawmaterials shall be used, then the said solid raw materials are dissolvedin an inert solvent. A suitable solvent is e.g. acetonitrile, or fullyor partially fluorinated alkanes like Pentafluorobutane (365 mfc),linear or cyclic partially or fully fluorinated ethers likeCF₃—CH₂—OCHF₂ (E245) or Octafluorotetrahydrofuran. Often, if availableor after a first synthesis, the product as such can also serve as inertsolvent, if liquid under the conditions. The direct fluorinationreaction, and/or the decarboxylation reaction, of the present inventioncan also be carried out in water, if the solid starting compound issoluble in water (H₂O).

In an alternative embodiment of the invention, it is also optionallydesired to employ another continuous flow reactor than a microreactor,preferably if, for example, the (halogenation promoting, e.g. thehalogenation or preferably the halogenation) catalyst composition usedin the halogenation or fluorination tends to get viscous during reactionor is viscous already as a said catalyst as such. In such case, acontinuous flow reactor, i.e. a device in which chemical reactions takeplace in a confinement with lower lateral dimensions of greater thanthat indicated above for a microreactor, i.e. of greater than about 1mm, but wherein the upper lateral dimensions are about ≤4 mm.Accordingly, in this alternative embodiment of the invention, employinga continuous flow reactor, the term “continuous flow reactor” preferablydenotes a device in which chemical reactions take place in a confinementwith typical lateral dimensions of from about ≥1 mm up to about ≤4 mm.In such an embodiment of the invention it is particularly preferred toemploy as a continuous flow reactor a plug flow reactor and/or a tubularflow reactor, with the said lateral dimensions. Also, in such anembodiment of the invention, as compared to the embodiment employing amicroreactor, it is particularly preferred to employ higher flow ratesin the continuous flow reactor, preferably in the plug flow reactorand/or a tubular flow reactor, with the said lateral dimensions. Forexample, such higher flow rates, are up to about 2 times higher, up toabout 3 times higher, up to about 4 times higher, up to about 5 timeshigher, up to about 6 times higher, up to about 7 times higher, or anyintermediate flow rate of from about ≥1 up to about ≤7 times higher, offrom about ≥1 up to about ≤6 times higher, of from about ≥1 up to about≤5 times higher, of from about ≥1 up to about ≤4 times higher, of fromabout ≥1 up to about ≤3 times higher, or of from about ≥1 up to about ≤2times higher, each as compared to the typical flow rates indicatedherein for a microreactor. Preferably, the said continuous flow reactor,more preferably the plug flow reactor and/or a tubular flow reactor,employed in this embodiment of the invention is configured with theconstruction materials as defined herein for the microreactors. Forexample, such construction materials are silicon carbide (SiC) and/orare alloys such as a highly corrosion resistantnickel-chromium-molybdenum-tungsten alloy, e.g. Hastelloy®, as describedherein for the microreactors.

A very particular advantage of the present invention employing amicroreactor, or a continuous flow reactor with the before said lateraldimensions, the number of separating steps can be reduced andsimplified, and may be devoid of time and energy consuming, e.g.intermediate, distillation steps. Especially, it is a particularadvantage of the present invention employing a microreactor, or acontinuous flow reactor with the before said lateral dimensions, thatfor separating simply phase separation methods can be employed, and thenon-consumed reaction components may be recycled into the process, orotherwise be used as a product itself, as applicable or desired.

In addition to the preferred embodiments of the present invention usinga microreactor according to the invention, in addition or alternativelyto using a microreactor, it is also possible to employ a plug flowreactor or a tubular flow reactor, respectively.

Plug flow reactor or tubular flow reactor, respectively, and theiroperation conditions, are well known to those skilled in the field.

Although the use of a continuous flow reactor with upper lateraldimensions of about ≤5 mm, or of about ≤4 mm, respectively, and inparticular of a microreactor, is particularly preferred in the presentinvention, depending on the circumstances, it could be imagined thatsomebody dispenses with an microreactor, then of course with yieldlosses and higher residence time, higher temperature, and instead takesa plug flow reactor or turbulent flow reactor, respectively. However,this could have a potential advantage, taking note of the mentionedpossibly disadvantageous yield losses, namely the advantage that theprobability of possible blockages (tar particle formation by non-idealdriving style) could be reduced because the diameters of the tubes orchannels of a plug flow reactor are greater than those of amicroreactor.

The possibly allegeable disadvantage of this variant using a plug flowreactor or a tubular flow reactor, however, may also be seen only assubjective point of view, but on the other hand under certain processconstraints in a region or at a production facility may still beappropriate, and loss of yields be considered of less importance or evenbeing acceptable in view of other advantages or avoidance ofconstraints.

In the following, the invention is more particularly described in thecontext of using a microreactor. Preferentially, a microreactor usedaccording to the invention is a ceramic continuous flow reactor, morepreferably a SiC (silicon carbide) continuous flow reactor, and can beused for material production at a multi-to scale. Within integrated heatexchangers and SiC materials of construction, it gives optimal controlof challenging flow chemistry application. The compact, modularconstruction of the flow production reactor enables, advantageously for:long term flexibility towards different process types; access to a rangeof production volumes (5 to 400 l/h); intensified chemical productionwhere space is limited; unrivalled chemical compatibility and thermalcontrol.

Ceramic (SiC) microreactors, are e.g. advantageously diffusion bonded 3MSiC reactors, especially braze and metal free, provide for excellentheat and mass transfer, superior chemical compatibility, of FDAcertified materials of construction, or of other drug regulatoryauthority (e.g. EMA) certified materials of construction. Siliconcarbide (SiC), also known as carborundum, is a containing silicon andcarbon, and is well known to those skilled in the art. For example,synthetic SiC powder is been mass-produced and processed for manytechnical applications.

For example, in the embodiments of the invention the objects areachieved by a method in which at least one reaction step takes place ina microreactor. Particularly, in preferred embodiments of the inventionthe objects are achieved by a method in which at least one reaction steptakes place in a microreactor that is comprising or is made of SiC(“SiC-microreactor”), or in a microreactor that is comprising or is madeof an alloy, e.g. such as Hastelloy C, as it is each defined hereinafter in more detail.

Thus, without being limited to, for example, in an embodiment of theinvention the microreactor suitable for, preferably for industrial,production an “SiC-microreactor” that is comprising or is made of SiC(silicon carbide; e.g. SiC as offered by Dow Corning as Type G1SiC or byChemtrix MR555 Plantrix), e.g. providing a production capacity of fromabout 5 up to about 400 kg per hour; or without being limited to, forexample, in another embodiment of the invention the microreactorsuitable for industrial production is comprising or is made of HastelloyC, as offered by Ehrfeld. Such microreactors are particularly suitablefor the, preferably industrial, production of fluorinated productsaccording to the invention.

In order to meet both the mechanical and chemical demands placed onproduction scale flow reactors, Plantrix modules are fabricated from 3M™SiC (Grade C). Produced using the patented 3M (EP 1 637 271 B1 andforeign patents) diffusion bonding technology, the resulting monolithicreactors are hermetically sealed and are free from welding lines/jointsand brazing agents. More technical information on the Chemtrix MR555Plantrix can be found in the brochure “CHEMTRIX—Scalable FlowChemistry—Technical Information Plantrix® MR555 Series,” published byChemtrix BV in 2017, which technical information is incorporated hereinby reference in its entirety.

Apart from the before said example, in other embodiments of theinvention, in general SiC from other manufactures, and as known to theskilled person, of course can be employed in the present invention.

Accordingly, in the present invention as microreactor also the Protrix®of by Chemtrix can be used. Protrix® is a modular, continuous flowreactor fabricated from 3M® silicon carbide, offering superior chemicalresistance and heat transfer. In order to meet both the mechanical andchemical demands placed on flow reactors, Protrix® modules arefabricated from 3M® SiC (Grade C). Produced using the patented 3M (EP 1637 271 B1 and foreign patents) diffusion bonding technology, theresulting monolithic reactors are hermetically sealed and are free fromwelding lines/joints and brazing agents. This fabrication technique is aproduction method that gives solid SiC reactors (thermal expansioncoefficient=4.1×10⁻⁶K⁻¹).

Designed for flow rates ranging from 0.2 to 20 ml/min and pressures upto 25 bar, Protrix® allows the user to develop continuous flow processesat the lab-scale, later transitioning to Plantrix® MR555 (×340 scalefactor) for material production. The Protrix® reactor is a unique flowreactor with the following advantages: diffusion bonded 3M® SiC moduleswith integrated heat exchangers that offer unrivaled thermal control andsuperior chemical resistance; safe employment of extreme reactionconditions on a g scale in a standard fumehood; efficient, flexibleproduction in terms of number of reagent inputs, capacity or reactiontime. The general specifications for the Protrix® flow reactors aresummarised as follows; possible reaction types are, e.g. A+B→P1+Q (orC)→P, wherein the terms “A”, “B” and “C” represent educts, “P” and “P1”products, and “Q” quencher; throughput (ml/min) of from about 0.2 up toabout 20; channel dimensions (mm) of 1×1 (pre-heat and mixer zone),1.4×1.4 (residence channel); reagent feeds of 1 to 3; module dimensions(width×height) (mm) of 110×260; frame dimensions (width×height×length)(mm) approximately 400×300×250; number of modules/frame is one (minimum)up to four (max.). More technical information on the ChemtrixProtrix®reactor can be found in the brochure “CHEMTRIX—Scalable FlowChemistry—Technical Information Protrix®,” published by Chemtrix BV in2017, which technical information is incorporated herein by reference inits entirety.

The Dow Corning as Type G1SiC microreactor, which is scalable forindustrial production, and as well suitable for process development andsmall production can be characterized in terms of dimensions as follows:typical reactor size (length×width×height) of 88 cm×38 cm×72 cm; typicalfluidic module size of 188 mm×162 mm. The features of the Dow Corning asType G1SiC microreactor can be summarized as follows: outstanding mixingand heat exchange: patented HEART design; small internal volume; highresidence time; highly flexible and multipurpose; high chemicaldurability which makes it suitable for high pH compounds and especiallyhydrofluoric acid; hybrid glass/SiC solution for construction material;seamless scale-up with other advanced-flow reactors. Typicalspecifications of the Dow Corning as Type G1SiC microreactor are asfollows: flow rate of from about 30 ml/min up to about 200 ml/min;operating temperature in the range of from about −60° C. up to about200° C., operating pressure up to about 18 barg (“barg” is a unit ofgauge pressure, i.e. pressure in bars above ambient or atmosphericpressure); materials used are silicon carbide, PFA (perfluoroalkoxyalkanes), perfluoroelastomer; fluidic module of 10 ml internal volume;options: regulatory authority certifications, e.g. FDA or EMA,respectively. The reactor configuration of Dow Corning as Type G1SiCmicroreactor is characterized as multipurpose and configuration can becustomized. Injection points may be added anywhere on the said reactor.

Hastelloy® C is an alloy represented by the formula NiCr21Mo14W,alternatively also known as “alloy 22” or “Hastelloy® C-22.” The saidalloy is well known as a corrosion resistantnickel-chromium-molybdenum-tungsten alloy and has excellent resistanceto oxidizing reducing and mixed acids. The said alloy is used in fluegas desulphurization plants, in the chemical industry, environmentalprotection systems, waste incineration plants, sewage plants. Apart fromthe before said example, in other embodiments of the invention, ingeneral nickel-chromium-molybdenum-tungsten alloy from othermanufactures, and as known to the skilled person, of course can beemployed in the present invention. A typical chemical composition (allin weight-%) of such nickel-chromium-molybdenum-tungsten alloy is, eachpercentage based on the total alloy composition as 100%: Ni (nickel) asthe main component (balance) of at least about 51.0%, e.g. in a range offrom about 51.0% to about 63.0%; Cr (chromium) in a range of from about20.0 to about 22.5%, Mo (molybdenum) in a range of from about 12.5 toabout 14.5%, W (tungsten or wolfram, respectively) in a range of fromabout 2.5 to about 3.5%; and Fe (iron) in an amount of up to about 6.0%,e.g. in a range of from about 1.0% to about 6.0%, preferably in a rangeof from about 1.5% to about 6.0%, more preferably in a range of fromabout 2.0% to about 6.0%. Optionally, the percentage based on the totalalloy composition as 100%, Co (cobalt) can be present in the alloy in anamount of up to about 2.5%, e.g. in a range of from about 0.1% to about2.5%. Optionally, the percentage based on the total alloy composition as100%, V (vanadium) can be present in the alloy in an amount of up toabout 0.35%, e.g. in a range of from about 0.1% to about 0.35%. Also,the percentage based on the total alloy composition as 100%, optionallylow amounts (i.e. ≤0.1%) of other element traces, e.g. independently ofC (carbon), Si (silicon), Mn (manganese), P (phosphor), and/or S(sulfur). In such case of low amounts (i.e. ≤0.1%) of other elements,the said elements e.g. of C (carbon), Si (silicon), Mn (manganese), P(phosphor), and/or S (sulfur), the percentage based on the total alloycomposition as 100%, each independently can be present in an amount ofup to about 0.1%, e.g. each independently in a range of from about 0.01to about 0.1%, preferably each independently in an amount of up to about0.08%, e.g. each independently in a range of from about 0.01 to about0.08%. For example, said elements e.g. of C (carbon), Si (silicon), Mn(manganese), P (phosphor), and/or S (sulfur), the percentage based onthe total alloy composition as 100%, each independently can be presentin an amount of, each value as an about value: C≤0.01%, Si≤0.08%,Mn≤0.05%, P≤0.015%, S≤0.02%. Normally, no traceable amounts of any ofthe following elements are found in the alloy compositions indicatedabove: Nb (niobium), Ti (titanium), Al (aluminum), Cu (copper), N(nitrogen), and Ce (cerium).

Hastelloy® C-276 alloy was the first wrought, nickel-chromium-molybdenummaterial to alleviate concerns over welding (by virtue of extremely lowcarbon and silicon contents). As such, it was widely accepted in thechemical process and associated industries, and now has a 50-year-oldtrack record of proven performance in a vast number of corrosivechemicals. Like other nickel alloys, it is ductile, easy to form andweld, and possesses exceptional resistance to stress corrosion crackingin chloride-bearing solutions (a form of degradation to which theaustenitic stainless steels are prone). With its high chromium andmolybdenum contents, it is able to withstand both oxidizing andnon-oxidizing acids, and exhibits outstanding resistance to pitting andcrevice attack in the presence of chlorides and other halides. Thenominal composition in weight-% is, based on the total composition as100%: Ni (nickel) 57% (balance); Co (cobalt) 2.5% (max.); Cr (chromium)16%; Mo (molybdenum) 16%; Fe (iron) 5%; W (tungsten or wolfram,respectively) 4%; further components in lower amounts can be Mn(manganese) up to 1% (max.); V (vanadium) up to 0.35% (max.); Si(silicon) up to 0.08% (max.); C (carbon) 0.01 (max.); Cu (copper) up to0.5% (max.).

In another embodiments of the invention, without being limited to, forexample, the microreactor suitable for the said production, preferablyfor the said industrial production, is an SiC-microreactor that iscomprising or is made only of SiC as the construction material (siliconcarbide; e.g. SiC as offered by Dow Corning as Type G1SiC or by ChemtrixMR555 Plantrix), e.g. providing a production capacity of from about 5 upto about 400 kg per hour.

It is of course possible according to the invention to use one or moremicroreactors, preferably one or more SiC-microreactors, in theproduction, preferably in the industrial production, of the fluorinatedproducts according to the invention. If more than one microreactor,preferably more than one SiC-microreactors, are used in the production,preferably in the industrial production, of the fluorinated productsaccording to the invention, then these microreactors, preferably theseSiC-microreactors, can be used in parallel and/or subsequentarrangements. For example, two, three, four, or more microreactors,preferably two, three, four, or more SiC-microreactors, can be used inparallel and/or subsequent arrangements.

For laboratory search, e.g. on applicable reaction and/or upscalingconditions, without being limited to, for example, as a microreactor thereactor type Plantrix of the company Chemtrix is suitable. Sometimes, ifgaskets of a microreactor are made out of other material than HDPTFE,leakage might occur quite soon after short time of operation because ofsome swelling, so HDPTFE gaskets secure long operating time ofmicroreactor and involved other equipment parts like settler anddistillation columns.

For example, an industrial flow reactor (“IFR”, e.g. Plantrix® MR555)comprises of SiC modules (e.g. 3M® SiC) housed within a (non-wetted)stainless steel frame, through which connection of feed lines andservice media are made using standard Swagelok fittings. The processfluids are heated or cooled within the modules using integrated heatexchangers, when used in conjunction with a service medium (thermalfluid or steam), and reacted in zig-zag or double zig-zag, meso-channelstructures that are designed to give plug flow and have a high heatexchange capacity. A basic IFR (e.g. Plantrix® MR555) system comprisesof one SiC module (e.g. 3M® SiC), a mixer (“MRX”) that affords access toA+B→P type reactions. Increasing the number of modules leads toincreased reaction times and/or system productivity. The addition of aquench Q/C module extends reaction types to A+B→P1+Q (or C)→P and ablanking plate gives two temperature zones. Herein the terms “A”, “B”and “C” represent educts, “P” and “P1” products, and “Q” quencher.

Typical dimensions of an industrial flow reactor (“IFR”, e.g. Plantrix®MR555) are, for example: channel dimensions in (mm) of 4×4 (“MRX”,mixer) and 5×5 (MRH-I/MRH-II; “MRH” denotes residence module); moduledimensions (width×height) of 200 mm×555 mm; frame dimensions(width×height) of 322 mm×811 mm. A typical throughput of an industrialflow reactor (“IFR”, e.g. Plantrix® MR555) is, for example, in the rangeof from about 50 l/h to about 400 l/h. in addition, depending on fluidproperties and process conditions used, the throughput of an industrialflow reactor (“IFR”, e.g. Plantrix® MR555), for example, can alsobe >400 l/h. The residence modules can be placed in series in order todeliver the required reaction volume or productivity. The number ofmodules that can be placed in series depends on the fluid properties andtargeted flow rate.

Typical operating or process conditions of an industrial flow reactor(“IFR”, e.g. Plantrix® MR555) are, for example: temperature range offrom about −30° C. to about 200° C.; temperature difference(service−process)<70° C.; reagent feeds of 1 to 3; maximum operatingpressure (service fluid) of about 5 bar at a temperature of about 200°C.; maximum operating pressure (process fluid) of about 25 bar at atemperature of about ≤200° C.

Further Aspects of the Invention:

In one aspect, the invention relates to a use of a fluorination gas,comprising or consisting of elemental fluorine (F₂), optionally whereinelemental fluorine (F₂) is present in a high concentration ofsubstantially more than, in particular very much more than 15% by volumeor in particular than 20% by volume of elemental fluorine (F₂),especially of equal to much higher than 25% by volume, i.e., at least25% by volume, of elemental fluorine (F₂), preferably of equal to muchhigher than 35% by volume or in particular than 45% by volume, for themanufacture of a fluorinated benzene in a liquid medium comprisingbenzoic acid as starting compound; preferably wherein the elementalfluorine (F₂) is present in the fluorination gas of b) in a highconcentration in a range of from 15-100% by volume, preferably within arange of from 20-100% by volume, more preferably within a range of from25-100% by volume, still more preferably within a range of from 30-100%by volume, even more preferably within a range of from 35-100% byvolume, an still more preferred within a range of from 45-100% byvolume, each based on the total volume of the fluorination gas as 100%by volume; characterized in that the starting compound is benzoic acid,and the fluorinated compound produced is a benzoic acid hypofluorite,which benzoic acid hypofluorite optionally subsequently isdecarboxylated to obtain a fluorinated benzene.

In a further aspect, the invention relates to a process for themanufacture of a benzoic acid hypofluorite by direct fluorination of abenzoic acid, wherein the process comprises the steps of a) to f) asdefined above and in claim 1, to obtain the benzoic acid hypofluorite,in situ or in isolated form.

In particular, according to the present invention the said process forthe manufacture of a benzoic acid hypofluorite, wherein the process isperformed according to the process as defined above for the directfluorination process based on the benzoic acid as the starting compound,and, for example, as defined in any of the claims 2 to 9 for the stepsa) to f).

In a still a further aspect, the invention relates to a use of a benzoicacid hypofluorite obtained, in situ or in isolated form, by directfluorination of a benzoic acid in a process comprising the steps of a)to f), as defined above, and, for example, as defined in claim 1, in themanufacture of a fluorinated benzene, preferably monofluorobenzene; inparticular by decarboxylation a benzoic acid hypofluorite; preferably byphotochemical decarboxylation, more preferably by photochemicaldecarboxylation by direct irradiation (λ>180 nm) or by light initiationin presence of a photosensitizer; and more preferably by photochemicaldecarboxylation by direct irradiation induced by a wavelength of λ>180nm.

In the said process for the manufacture of a fluorinated benzene,preferably monofluorobenzene, according to the invention as describedabove, and for example in claims 1 to 9, in step g) the decarboxylationof benzoic acid hypofluorite is carried out by photochemicaldecarboxylation; more preferably by photochemical decarboxylation bydirect irradiation (λ>180 nm) or by light initiation in presence of aphotosensitizer; and most preferably by photochemical decarboxylation bydirect irradiation induced by a wavelength of λ>180 nm.

Finally, the invention in one aspect also relates to a process for themanufacture of a fluorinated benzene, preferably monofluorobenzene,wherein a benzoic acid hypofluorite is converted into a fluorinatedbenzene by decarboxylation; in particular by photochemicaldecarboxylation; preferably by photochemical decarboxylation; morepreferably by photochemical decarboxylation by direct irradiation (λ>180nm) or by light initiation in presence of a photosensitizer; and mostpreferably by photochemical decarboxylation by direct irradiationinduced by a wavelength of λ>180 nm.

The following examples are intended to further illustrate the inventionwithout limiting its scope.

EXAMPLES

In the following examples a fluorobenzene was prepared from a benzoicacid hypofluorite obtained by direct fluorination with a fluorinationgas, preferably with a fluorination gas with high concentration ofelemental fluorine (F₂), according to this invention, and subsequentdecarboxylation, and according to the reaction Schemes given above inthe description.

Representative, example procedures are described hereinafter in theembodiment following examples.

The examples are carried out in a representative scale of 200 g benzoicacid as a starting compound. Experiments were carried out in thereaction time frames as given in the description above, to yield theproduct quantities and conversion rates given below in the examples.Quantities of benzoic acid as a starting compound and/or reaction timesmay be easily adapted to produce the fluorinated products in large-scaleand/or industrial production, e.g., benzoic acid hypofluorite and/orsubsequently of fluorinated benzene, preferably monofluorobenzene.Accordingly, adapting

Quantities of benzoic acid as a starting compound and/or reaction timesmay be easily adapted to at least about 1 kg of benzoic acid as thestarting material is fluorinated per hour, preferably at least about 1.5kg of benzoic acid as the starting material is fluorinated (e.g., lessthan 10 hours, or even less than 5 hours), to yield benzoic acidhypofluorite, and/or subsequently a fluorinated benzene, preferablymonofluorobenzene, with a conversion of at least 80%, in particular ofat least 85%, preferably about at least 90%, more preferably about atleast 95% conversion.

Example 1

Synthesis of benzoic acid hypofluorite in CH₃CN as solvent.

In a 1 l counter-current system out of Hastelloy C4 like in the schemedescribed above, 200 g (1.64 mol) Benzoic acid is dissolved in 200 mlCH₃CN (will not be fluorinated as benzoic acid is much more reactive)and circulated over the tower filled with (inert) plastic fillings. 68.4g (1.80 mol) F₂-gas (20% in N₂) from a cylinder is fed at roomtemperature into the circulating mixture, formed HF is mainly (but notcompletely) leaving together with the N₂-stream over the top.

In the counter-current system the F₂-gas pressure (taken out of thepressure bottle), of course, was adjusted to compensate for the backpressure of the liquid medium level, and for pressing the F₂-gas throughthe liquid medium contained in the reactor. Accordingly, some backpressure through the liquid level is compensated by an F₂-gas pressureof no more than usually from about 2 bar (abs.) up to a maximum of about3 bar (abs.).

Example 2

Pyrolysis of Benzoic Acid Hypofluorite.

100 g of the solution obtained in example 1 is pyrolyzed within 2 h at200° C. in a 250 ml Roth autoclave made out of 1.4571, the autoclavecontained 10 g Ni-fillings as catalyst). It was not tested if thereaction is also workable without nickel initiation. The pressure waskept at 20 bar by an automatic valve releasing overpressure created byformed CO₂. The resulting solution was washed with water, dried overNa₂SO₄ and subjected to a fine distillation over a distillation tower atatmospheric pressure over 5 h. 40.6 g fluorobenzene (92% of theory) wereisolated at 85° C. as yellow liquid. As Acetonitrile and fluorobenzenehave quite close boiling points, a very careful heating and distillationis essential.

Example 3

Pyrolysis of a Concentrated Solution of Benzoic Acid Hypofluorite.

100 g of the solution obtained in example 1 was concentrated by removingexcess Acetonitrile at a rotavapor (plastic flask) at room temperatureat 20 mbar. The remaining oil was pyrolyzed like described in example 2.The obtained yield in fluorobenzene was 42.8 g (97% of theory).

Example 4

Purification of Benzoic Acid Hypofluorite.

The solution obtained in example 1 was concentrated by removing excessacetonitrile at a rotavapor (plastic flask) at room temperature at 20mbar like in example 3. The remaining oil now was fine distilled. 215.9g benzoic acid hypofluorite was obtained at 51° C. transitiontemperature at 20 mbar (yield: 94% of theory).

Example 5

Pyrolysis of a Purified Benzoic Acid Hypofluorite Sample.

100 g (0.71 mol) of the purified benzoic acid hypofluorite out ofexample 4 was pyrolyzed like described in example 2. The obtained yieldin fluorobenzene was 68.2 g (99% of theory).

Example 6

Synthesis of Benzoic Acid Hypofluorite in H₂O as Solvent.

In a 11 countercurrent system out of Hastelloy C4 like in the schemedescribed above, 200 g (1.64 mol)benzoic acid is dissolved in 200 ml H₂Oand circulated over the tower filled with plastic fillings. 68.4 g (1.80mol) F₂-gas (20% in N₂) from a cylinder is fed at room temperature intothe circulating mixture, formed HF is kept in the water, the N₂-streamis leaving together with the little excess of F₂-gas over the top of theapparatus. After having finished the F₂-feed, the decarboxylation isdone as described in example 7.

Example 7

Decarboxylation of Benzoic Acid Hypofluorite in H₂O.

100 g of the mixture as prepared in example 6 is transferred to a 250 mlRoth autoclave made out of 1.4571 high grade stainless steel containingNi-fillings and heated to 200° C. for 2 h. The pressure was kept at 20bar by an automatic valve releasing overpressure created by formed CO₂.After cooling down the resulting mixture is extracted with CH₂Cl₂ toobtain 40.1 g (91% of theory) fluorobenzene of 99% purity (GC) afterremoving the CH₂C₁₂ (together still with some little HF) bydistillation.

Example 8

Photochemical Induced Decarboxylation.

The mixture obtained in example 6 was filtered to remove (little)particles and filled into a photoreactor equipped with a TQ 718 Hg highpressure lamp in a double wall quarz tube. The outer quarz tube which isin contact with the reaction media is covered with a FEP shrinking pipe(seehttps://www.polyfluor.nl/produkte/schrumpfschlauche/fep-schrumpfschlauche/)to avoid fluoride corrosion. The lamp itself (inside the double wall)was cooled by a flow of compressed air, the outer sphere of thephotoreactor is made out of PE and has a double jacket and which iscooled with water so that the total reactor content is kept at or below40° C. A very slow flow of N₂-gas was fed through the solution and wasleaving over a bubble counter. The solution was now irradiated for 1 hat atmospheric pressure and in a temperature range between 30 and 40°C.; CO₂ evolution could be recognized at the bubble counter (observedafter stopping the N₂-gas feed from time to time). The resulting mixtureis extracted with CH₂Cl₂ to obtain 140.2 g (89% of theory) fluorobenzeneof 99.2% purity (GC) after removing the CH₂Cl₂ (together still with someHF) by distillation.

Example 9

Continuous Photochemical Induced Decarboxylation in a Coil Reactor (FEPPipe).

The mixture obtained on example 1 is fed at 2 bar abs. continuously with100 ml/h through an FEP pipe of 5 mm diameter (seehttps://www.polyfluor.nl/de/produkte/-fluorkunststoff-schlauche/fep-schlauche/)and 1 m length and forms a coil. The irradiation was done by putting thecoil into a RayonettRPR-100 irradiation reactor (supplier: “The SouthernNew England Ultraviolet Company”) equipped with 254 nm lamps. Thecomposition after having passed the 1 m FEP pipe showed a conversion of82% and a selectivity to fluorobenzene of 97%.

Example 10

Continuous Hypofluorite Preparation and Decarboxylation in MicroreactorSystem.

Scheme for a microreactor system for first and second step is shown inFIG. 2.

In Scheme 2, the first microreactor I is made out of stainless steel orSiC, and the microreactor II is made out of nickel.

The mixture obtained in example 1 is fed continuously with 250 ml/h, anda corresponding amount F₂-gas (20% in N₂) per hour from a cylinder,through a 27 ml microreactor from Chemtrix kept with cooling at 30° C.The microreactor I leaving material showed a conversion of 98% tobenzoic acid hypofluorite. Afterwards the flow enters the secondmicroreactor II of same volume made out of nickel and heated to 200° C.For microreactor II, Innosyn BV (Geelen, Netherlands) was chosen assupplier. All the material coming out of microreactor 2 was collected ina stainless steel cylinder (reservoir) and carefully distilled at roomtemperature to yield 83% fluorobenzene.

Example 11

Continuous Hypofluorite Preparation in Microreactor Combined WithContinuous Decarboxylation in Coil Reactor.

Example 10 was repeated, but the second microreactor was replaced by theFEP coil reactor as in example 9. At pressure of 2 bar abs. themicroreactor I leaving mixture enters the FEP coil put into a SouthernNew England Ultraviolet Company's Rayonett with 254 nm lamps. Theconversion of benzoic acid was quantitative, and the isolated yield offluorobenzene was 87%.

Example 12

Experiment done like example 10, but in water as solvent. After coolingdown fluorobenzene separated as second phase from a water phasecontaining the majority of the HF. The yield of fluorobenzene was 93%.

Example 13

Experiment done like example 11, but in water as solvent. After coolingdown fluorobenzene also separated as second phase from a water phasecontaining the majority of the HF. The yield of fluorobenzene was 97%.

What is claimed is:
 1. A process for the manufacture of a fluorinatedbenzene, wherein the process comprises a plurality of steps of: a)provision of a liquid medium comprising benzoic acid as startingcompound; b) provision of a fluorination gas comprising elementalfluorine, wherein the fluorine is present in the fluorination gas in aconcentration equal to or more than 20% by volume; c) provision of afirst reactor or reactor system, resistant to elemental fluorine andhydrogen fluoride; d) in a step of direct fluorination, passing thefluorination gas of b), in a reactor or reactor system of c), throughthe liquid medium of a) comprising the benzoic acid as startingcompound, and thereby reacting the benzoic acid starting compound withthe elemental fluorine of the fluorination gas a) to substitute in thehydrogen atom in the benzoic acid carboxlylic group for fluorine, andwherein the reaction is carried out at temperature of from about −30° C.to about +100° C. and a pressure of from about 1 bar absolute to about10 bar absolute bar; e) withdrawing the benzoic acid hypofluorite formedin the direct fluorination step d) from the reactor or reactor system ofc); f) to obtain the benzoic acid hypofluorite, in situ or in isolatedform; and g) subjecting the benzoic acid hypofluorite obtained in stepf), in situ or in isolated form, in a second reactor or reactor systemto decarboxylation, to thereby obtain the fluorinated benzene.
 2. Theprocess for the manufacture of a fluorinated a fluorinated benzeneaccording to claim 1, wherein the elemental fluorine is present in thefluorination gas of b) in a concentration of at least 25% by volumebased on the total volume of the fluorination gas as 100% by volume. 3.The process for the manufacture of a fluorinated benzene according toclaim 2, wherein the elemental fluorine is present in the fluorinationgas of b) in a concentration within a range from 30-100% by volume basedon the total volume of the fluorination gas as 100% by volume.
 4. Theprocess for the manufacture of a fluorinated benzene according to claim1, wherein the reaction in step d) is carried out in a column reactor,wherein the liquid medium of a) comprising the benzoic acid as thestarting compound is circulated in a loop, while the fluorination gas ofb) comprising elemental fluorine (F₂), is fed into the column reactor ofc) and in step d) is passed through the liquid medium to react with thestarting compound benzoic acid wherein the loop is operated with acirculation velocity of from 1,500 l/h to 5,000 l/h.
 5. The process forthe manufacture of a fluorinated benzene according to claim 4, whereinthe column reactor is equipped with at least one of the following: (i)at least one cooler, at least one liquid reservoir, with inlet andoutlet for, and containing the liquid medium of a) comprising benzoicacid as the starting compound; (ii) a pump for pumping and circulatingthe liquid medium of a); (iii) one or more jets placed at the top of thecolumn reactor, for spraying the circulating medium of a) into thecolumn reactor; (iv) one or more feeding inlets for introducing thefluorination gas of b) comprising elemental fluorine (F₂) into thecolumn reactor; (v) one or more sieves placed at the bottom of thecolumn reactor; and (vi) at least one gas outlet equipped with apressure valve, and at least one outlet for withdrawing the benzoic acidhypofluorite, for in situ or in isolated form, in step e).
 6. Theprocess for the manufacture of a fluorinated benzene according to claim4, wherein column reactor is a packed bed tower reactor which is packedwith fillers resistant to elemental fluorine and hydrogen fluoride. 7.The process for the manufacture of a fluorinated benzene according toclaim 4, wherein the reaction is carried out with a counter-current flowof the circulating liquid medium of a) comprising the benzoic acid asstarting compound and of the fluorination gas of b) fed into the columnreactor and which fluorination gas of b) is comprising elementalfluorine (F₂).
 8. The process for the manufacture of a fluorinatedbenzene according to claim 1, wherein the reaction is carried out in atleast one step as a continuous process, wherein the continuous processis performed in at least one microreactor; wherein of the said steps atleast the step of a fluorination reaction is a continuous process in atleast one microreactor under one or more of the following conditions:flow rate: of from about 10 ml/h up to about 400 l/h; temperature: offrom about 30° C. up to about 150° C.; pressure: of from about 4 bar upto about 50 bar; residence time: of from about 1 second up to about 60minutes.
 9. The process of preparing a fluorinated benzene according toclaim 8, wherein at least one of the microreactors, independently is aSiC-microreactor.
 10. A process for the manufacture of a benzoic acidhypofluorite by direct fluorination of a benzoic acid, wherein theprocess comprises a plurality of steps of a) to f), to obtain thebenzoic acid hypofluorite, in situ or in isolated form; wherein thesteps of a) to f) comprises: a) provision of a liquid medium comprisingbenzoic acid as starting compound; b) provision of a fluorination gascomprising elemental fluorine wherein the fluorine is present in thefluorination gas in a concentration equal to or more than 20% by volume;c) provision of a first reactor or reactor system, resistant toelemental fluorine and hydrogen fluoride; d) in a step of directfluorination, passing the fluorination gas of b), in a reactor orreactor system of c), through the liquid medium of a) comprising thebenzoic acid as starting compound, and thereby reacting the benzoic acidstarting compound with the elemental fluorine of the fluorination gas a)to substitute in the hydrogen atom in the benzoic acid carboxlylic groupfor fluorine, and wherein the reaction is carried out at temperature offrom about −30° C. to about +100° C. and a pressure of from about 1 barabsolute to about 10 bar absolute bar; e) withdrawing the benzoic acidhypofluorite formed in the direct fluorination step d) from the reactoror reactor system of c); and f) to obtain the benzoic acid hypofluorite,in situ or in isolated form.
 11. The process for the manufacture of abenzoic acid hypofluorite according to claim 10, wherein the elementalfluorine is present in the fluorination gas of b) in a concentration ofat least 25% by volume based on the total volume of the fluorination gasas 100% by volume.
 12. The process for the manufacture of a fluorinatedbenzene, according to claim 1, wherein in step g) the decarboxylation ofbenzoic acid hypofluorite is carried out by photochemicaldecarboxylation by direct irradiation induced by a wavelength of λ>180nm.
 13. The process for the manufacture of a fluorinated benzeneaccording to claim 2, wherein the elemental fluorine is present in thefluorination gas of b) in a concentration of at least 35% by volumebased on the total volume of the fluorination gas as 100% by volume. 14.The process for the manufacture of a fluorinated benzene according toclaim 13, wherein the elemental fluorine is present in the fluorinationgas of b) in a concentration of at least 45% by volume based on thetotal volume of the fluorination gas as 100% by volume.
 15. The processfor the manufacture of a fluorinated benzene according to claim 4,wherein the loop is operated with a circulation velocity of from 3,500l/h to 4,500 l/h.
 16. The process for the manufacture of a fluorinatedbenzene according to claim 6, wherein the packed bed tower reactor ispacked with Raschig fillers or metal fillers.
 17. The process for themanufacture of a fluorinated benzene according to claim 6, wherein thepacked bed tower reactor is a gas scrubber system.
 18. The process forthe manufacture of a fluorinated benzene according to claim 11, whereinthe elemental fluorine is present in the fluorination gas of b) in aconcentration of at least 35% by volume based on the total volume of thefluorination gas as 100% by volume.
 19. The process for the manufactureof a fluorinated benzene according to claim 18, wherein the elementalfluorine is present in the fluorination gas of b) in a concentration ofat least 45% by volume based on the total volume of the fluorination gasas 100% by volume.